Twin and family studies in autistic disorders (AD) have elucidated a high heritability of the narrow and broad phenotype of AD. In this review on the genetics of AD, we will initially delineate the phenotype of AD and discuss aspects of differential diagnosis, which are particularly relevant with regard to the genetics of autism. Cytogenetic and molecular genetic studies will be presented in detail, and the possibly involved aetiopathological pathways will be described. Implications of the different genetic findings for genetic counselling will be mentioned.
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American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. American Psychiatric Association: Washington, DC, 1994.
World Health Organisation. The ICD-10 Classification of Mental and Behavioural Disorders. Clinical Descriptions and Diagnostic Guidelines. World Health Organisation: Geneva, 1992.
Kanner L . Autistic disturbance of affective contact. Nervous Child 1943; 2: 217–250.
Asperger H . Die ‘Autistischen Psychopathen’ im Kindesalter. Arch Psychiat Nerven 1944; 117: 73–136.
Rutter M . Concepts of autism: a review of research. J Child Psychol Psychiatry 1968; 9: 1–25.
Wing L . Asperger's syndrome: a clinical account. Psychol Med 1981; 11: 115–129.
Percy AK, Lane JB . Rett syndrome: clinical and molecular update. Curr Opin Pediatr 2004; 16: 670–677.
Erlandson A, Hagberg B . MECP2 abnormality phenotypes: clinicopathologic area with broad variability. J Child Neurol 2005; 20: 727–732.
Fombonne E . Epidemiological surveys of autism and other pervasive developmental disorders: an update. J Autism Dev Disord 2003; 33: 365–382.
Volkmar FR, Lord C, Bailey A, Schultz RT, Klin A . Autism and pervasive developmental disorders. J Child Psychol Psychiatry 2004; 45: 135–170.
Gillberg C . Chromosomal disorders and autism. J Autism Dev Disord 1998; 28: 415–425.
Lauritsen M, Mors O, Mortensen PB, Ewald H . Infantile autism and associated autosomal chromosome abnormalities: a register-based study and a literature survey. J Child Psychol Psychiatry 1999; 40: 335–345.
Reddy KS . Cytogenetic abnormalities and fragile-X syndrome in autism spectrum disorder. BMC Med Genet 2005; 6: 3–19.
Chakrabarti S, Fombonne E . Pervasive developmental disorders in preschool children. JAMA 2001; 285: 3093–3099.
Ritvo ER, Mason-Brothers A, Freeman BJ, Pingree C, Jenson WR, McMahon WM et al. The UCLA – University of Utah epidemiologic survey of autism: the etiologic role of rare diseases. Am J Psychiatry 1990; 147: 1614–1621.
Wassink TH, Piven J, Patil SR . Chromosomal abnormalities in a clinic sample of individuals with autistic disorder. Psychiatr Genet 2001; 11: 57–63.
Wassink TH, Piven J, Vieland VJ, Huang J, Swiderski RE, Pietila J et al. Evidence supporting WNT2 as an autism susceptibility gene. Am J Med Genet 2001; 105: 406–413.
Vorstman JA, Staal WG, van Daalen E, van Engeland H, Hochstenbach PF, Franke L . Identification of novel autism candidate regions through analysis of reported cytogenetic abnormalities associated with autism. Mol Psychiatry 2006; 11, 1–18, 28.
Bolton PF, Dennis NR, Browne CE, Thomas NS, Veltman MW, Thompson RJ et al. The phenotypic manifestations of interstitial duplications of proximal 15q with special reference to the autistic spectrum disorders. Am J Med Genet 2001; 105: 675–685.
Borgatti R, Piccinelli P, Passoni D, Dalpra L, Miozzo M, Micheli R et al. Relationship between clinical and genetic features in ‘inverted duplicated chromosome 15’ patients. Pediatr Neurol 2001; 24: 111–116.
Gurrieri F, Battaglia A, Torrisi L, Tancredi R, Cavallaro C, Sangiorgi E et al. Pervasive developmental disorder and epilepsy due to maternally derived duplication of 15q11–q13. Neurology 1999; 52: 1694–1697.
Repetto GM, White LM, Bader PJ, Johnson D, Knoll JH . Interstitial duplications of chromosome region 15q11q13: clinical and molecular characterization. Am J Med Genet 1998; 79: 82–89.
Schroer RJ, Phelan MC, Michaelis RC, Crawford EC, Skinner SA, Cuccaro M et al. Autism and maternally derived aberrations of chromosome 15q. Am J Med Genet 1998; 76: 327–336.
Sutcliffe JS, Nurmi EL, Lombroso PJ . Genetics of childhood disorders: XLVII. Autism, part 6: duplication and inherited susceptibility of chromosome 15q11–q13 genes in autism. J Am Acad Child Adolesc Psychiatry 2003; 42: 253–256.
Thomas JA, Johnson J, Peterson Kraai TL, Wilson R, Tartaglia N, LeRoux J et al. Genetic and clinical characterization of patients with an interstitial duplication 15q11–q13, emphasizing behavioral phenotype and response to treatment. Am J Med Genet A 2003; 119: 111–120.
Wolpert CM, Menold MM, Bass MP, Qumsiyeh MB, Donnelly SL, Ravan SA et al. Three probands with autistic disorder and isodicentric chromosome 15. Am J Med Genet 2000; 96: 365–372.
Laan LA, Vein AA . Angelman syndrome: is there a characteristic EEG? Brain Dev 2005; 27: 80–87.
Valente KD, Koiffmann CP, Fridman C, Varella M, Kok F, Andrade JQ et al. Epilepsy in patients with Angelman syndrome caused by deletion of the chromosome 15q11-13. Arch Neurol 2006; 63: 122–128.
Clayton-Smith J, Laan L . Angelman syndrome: a review of the clinical and genetic aspects. J Med Genet 2003; 40: 87–95.
State MW, Dykens EM . Genetics of childhood disorders: XV. Prader–Willi syndrome: genes, brain, and behavior. J Am Acad Child Adolesc Psychiatry 2000; 39: 797–800.
Vogels A, Fryns JP . The Prader–Willi syndrome and the Angelman syndrome. Genet Counsel 2002; 13: 385–396.
Milner KM, Craig EE, Thompson RJ, Veltman MW, Thomas NS, Roberts S et al. Prader–Willi syndrome: intellectual abilities and behavioural features by genetic subtype. J Child Psychol Psychiatry 2005; 46: 1089–1096.
Casas KA, Mononen TK, Mikail CN, Hassed SJ, Li S, Mulvihill JJ et al. Chromosome 2q terminal deletion: report of 6 new patients and review of phenotype–breakpoint correlations in 66 individuals. Am J Med Genet A 2004; 130: 331–339.
Gallagher L, Becker K, Kearney G, Dunlop A, Stallings R, Green A et al. Brief report: a case of autism associated with del(2)(q32.1q32.2) or (q32.2q32.3). J Autism Dev Disord 2003; 33: 105–108.
Ghaziuddin M, Burmeister M . Deletion of chromosome 2q37 and autism: a distinct subtype? J Autism Dev Disord 1999; 29: 259–263.
Lukusa T, Vermeesch JR, Holvoet M, Fryns JP, Devriendt K . Deletion 2q37.3 and autism: molecular cytogenetic mapping of the candidate region for autistic disorder. Genet Counsel 2004; 15: 293–301.
Smith M, Escamilla JR, Filipek P, Bocian ME, Modahl C, Flodman P et al. Molecular genetic delineation of 2q37.3 deletion in autism and osteodystrophy: report of a case and of new markers for deletion screening by PCR. Cytogenet Cell Genet 2001; 94: 15–22.
Wassink TH, Piven J, Vieland VJ, Jenkins L, Frantz R, Bartlett CW et al. Evaluation of the chromosome 2q37.3 gene CENTG2 as an autism susceptibility gene. Am J Med Genet B 2005; 136: 36–44.
Wolff DJ, Clifton K, Karr C, Charles J . Pilot assessment of the subtelomeric regions of children with autism: detection of a 2q deletion. Genet Med 2002; 4: 10–14.
Ashley-Koch A, Wolpert CM, Menold MM, Zaeem L, Basu S, Donnelly SL et al. Genetic studies of autistic disorder and chromosome 7. Genomics 1999; 61: 227–236.
Vincent JB, Herbrick JA, Gurling HM, Bolton PF, Roberts W, Scherer SW . Identification of a novel gene on chromosome 7q31 that is interrupted by a translocation breakpoint in an autistic individual. Am J Hum Genet 2000; 67: 510–514.
Warburton P, Baird G, Chen W, Morris K, Jacobs BW, Hodgson S et al. Support for linkage of autism and specific language impairment to 7q3 from two chromosome rearrangements involving band 7q31. Am J Med Genet 2000; 96: 228–234.
Fine SE, Weissman A, Gerdes M, Pinto-Martin J, Zackai EH, McDonald-McGinn DM et al. Autism spectrum disorders and symptoms in children with molecularly confirmed 22q11.2 deletion syndrome. J Autism Dev Disord 2005; 35: 461–470.
Ogilvie CM, Moore J, Daker M, Palferman S, Docherty Z . Chromosome 22q11 deletions are not found in autistic patients identified using strict diagnostic criteria. IMGSAC. International Molecular Genetics Study of Autism Consortium. Am J Med Genet 2000; 96: 15–17.
Manning MA, Cassidy SB, Clericuzio C, Cherry AM, Schwartz S, Hudgins L et al. Terminal 22q deletion syndrome: a newly recognized cause of speech and language disability in the autism spectrum. Pediatrics 2004; 114: 451–457.
Roach ES, Sparagana SP . Diagnosis of tuberous sclerosis complex. J Child Neurol 2004; 19: 643–649.
Harrison JE, Bolton PF . Annotation: tuberous sclerosis. J Child Psychol Psychiatry 1997; 38: 603–614.
Lewis JC, Thomas HV, Murphy KC, Sampson JR . Genotype and psychological phenotype in tuberous sclerosis. J Med Genet 2004; 41: 203–207.
Bolton PF, Griffiths PD . Association of tuberous sclerosis of temporal lobes with autism and atypical autism. Lancet 1997; 349: 392–395.
Bolton PF, Park RJ, Higgins JN, Griffiths PD, Pickles A . Neuro-epileptic determinants of autism spectrum disorders in tuberous sclerosis complex. Brain 2002; 125: 1247–1255.
Gutierrez GC, Smalley SL, Tanguay PE . Autism in tuberous sclerosis complex. J Autism Dev Disord 1998; 28: 97–103.
Hunt A, Dennis J . Psychiatric disorder among children with tuberous sclerosis. Dev Med Child Neurol 1987; 29: 190–198.
Jambaque I, Chiron C, Dumas C, Mumford J, Dulac O . Mental and behavioural outcome of infantile epilepsy treated by vigabatrin in tuberous sclerosis patients. Epilepsy Res 2000; 38: 151–160.
Cianchetti C, Sannio-Fancello G, Fratta AL, Manconi F, Orano A, Pischedda MP et al. Neuropsychological, psychiatric, and physical manifestations in 149 members from 18 fragile X families. Am J Med Genet 1991; 40: 234–243.
Lombroso PJ . Genetics of childhood disorders: XLVIII. Learning and memory. Part 1: Fragile X syndrome update. J Am Acad Child Adolesc Psychiatry 2003; 42: 372–375.
Oostra BA, Chiurazzi P . The fragile X gene and its function. Clin Genet 2001; 60: 399–408.
Sutcliffe JS, Nelson DL, Zhang F, Pieretti M, Caskey CT, Saxe D et al. DNA methylation represses FMR-1 transcription in fragile X syndrome. Hum Mol Genet 1992; 1: 397–400.
Bailey AJ . The biology of autism. Psychol Med 1993; 23: 7–11.
Hallmayer J, Pintado E, Lotspeich L, Spiker D, McMahon W, Petersen PB et al. Molecular analysis and test of linkage between the FMR-1 gene and infantile autism in multiplex families. Am J Hum Genet 1994; 55: 951–959.
Vincent JB, Thevarkunnel S, Kolozsvari D, Paterson AD, Roberts W, Scherer SW . Association and transmission analysis of the FMR1 IVS10+14C-T variant in autism. Am J Med Genet B 2004; 125: 54–56.
Klauck SM, Munstermann E, Bieber-Martig B, Ruhl D, Lisch S, Schmotzer G et al. Molecular genetic analysis of the FMR-1 gene in a large collection of autistic patients. Hum Genet 1997; 100: 224–229.
Gurling HM, Bolton PF, Vincent J, Melmer G, Rutter M . Molecular and cytogenetic investigations of the fragile X region including the Frax A and Frax E CGG trinucleotide repeat sequences in families multiplex for autism and related phenotypes. Hum Hered 1997; 47: 254–262.
Irons M, Elias ER, Salen G, Tint GS, Batta AK . Defective cholesterol biosynthesis in Smith–Lemli–Opitz syndrome. Lancet 1993; 341: 1414.
Tint GS, Irons M, Elias ER, Batta AK, Frieden R, Chen TS et al. Defective cholesterol biosynthesis associated with the Smith–Lemli–Opitz syndrome. N Engl J Med 1994; 330: 107–113.
Tierney E, Nwokoro NA, Porter FD, Freund LS, Ghuman JK, Kelley RI . Behavior phenotype in the RSH/Smith–Lemli–Opitz syndrome. Am J Med Genet 2001; 98: 191–200.
Ryan AK, Bartlett K, Clayton P, Eaton S, Mills L, Donnai D et al. Smith–Lemli–Opitz syndrome: a variable clinical and biochemical phenotype. J Med Genet 1998; 35: 558–565.
Cunniff C, Kratz LE, Moser A, Natowicz MR, Kelley RI . Clinical and biochemical spectrum of patients with RSH/Smith–Lemli–Opitz syndrome and abnormal cholesterol metabolism. Am J Med Genet 1997; 68: 263–269.
Sikora DM, Pettit-Kekel K, Penfield J, Merkens LS, Steiner RD . The near universal presence of autism spectrum disorders in children with Smith–Lemli–Opitz syndrome. Am J Med Genet A 2006; 140: 1511–1518.
Folstein SE, Rosen-Sheidley B . Genetics of autism: complex aetiology for a heterogeneous disorder. Nat Rev Genet 2001; 2: 943–955.
Stromland K, Nordin V, Miller M, Akerstrom B, Gillberg C . Autism in thalidomide embryopathy: a population study. Dev Med Child Neurol 1994; 36: 351–356.
Moore SJ, Turnpenny P, Quinn A, Glover S, Lloyd DJ, Montgomery T et al. A clinical study of 57 children with fetal anticonvulsant syndromes. J Med Genet 2000; 37: 489–497.
Williams G, King J, Cunningham M, Stephan M, Kerr B, Hersh JH . Fetal valproate syndrome and autism: additional evidence of an association. Dev Med Child Neurol 2001; 43: 202–206.
Aronson M, Hagberg B, Gillberg C . Attention deficits and autistic spectrum problems in children exposed to alcohol during gestation: a follow-up study. Dev Med Child Neurol 1997; 39: 583–587.
Nanson JL . Autism in fetal alcohol syndrome: a report of six cases. Alcohol Clin Exp Res 1992; 16: 558–565.
Chess S, Fernandez P, Korn S . Behavioral consequences of congenital rubella. J Pediatr 1978; 93: 699–703.
Chess S . Follow-up report on autism in congenital rubella. J Autism Child Schizophr 1977; 7: 69–81.
Wakefield AJ, Murch SH, Anthony A, Linnell J, Casson DM, Malik M et al. Ileal–lymphoid–nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet 1998; 351: 637–641.
Chen W, Landau S, Sham P, Fombonne E . No evidence for links between autism, MMR and measles virus. Psychol Med 2004; 34: 543–553.
Honda H, Shimizu Y, Rutter M . No effect of MMR withdrawal on the incidence of autism: a total population study. J Child Psychol Psychiatry 2005; 46: 572–579.
Smeeth L, Cook C, Fombonne E, Heavey L, Rodrigues LC, Smith PG et al. MMR vaccination and pervasive developmental disorders: a case–control study. Lancet 2004; 364: 963–969.
Taylor B, Miller E, Farrington CP, Petropoulos MC, Favot-Mayaud I, Li J et al. Autism and measles, mumps, and rubella vaccine: no epidemiological evidence for a causal association. Lancet 1999; 353: 2026–2029.
Bailey A, Le Couteur A, Gottesman I, Bolton P, Simonoff E, Yuzda E et al. Autism as a strongly genetic disorder: evidence from a British twin study. Psychol Med 1995; 25: 63–77.
Folstein S, Rutter M . Infantile autism: a genetic study of 21 twin pairs. J Child Psychol Psychiatry 1977; 18: 297–321.
Ritvo ER, Spence MA, Freeman BJ, Mason-Brothers A, Mo A, Marazita ML . Evidence for autosomal recessive inheritance in 46 families with multiple incidences of autism. Am J Psychiatry 1985; 142: 187–192.
Steffenburg S, Gillberg C, Hellgren L, Andersson L, Gillberg IC, Jakobsson G et al. A twin study of autism in Denmark, Finland, Iceland, Norway and Sweden. J Child Psychol Psychiatry 1989; 30: 405–416.
Betancur C, Leboyer M, Gillberg C . Increased rate of twins among affected sibling pairs with autism. Am J Hum Genet 2002; 70: 1381–1383.
Greenberg DA, Hodge SE, Sowinski J, Nicoll D . Excess of twins among affected sibling pairs with autism: implications for the etiology of autism. Am J Hum Genet 2001; 69: 1062–1067.
Croen LA, Grether JK, Selvin S . Descriptive epidemiology of autism in a California population: who is at risk? J Autism Dev Disord 2002; 32: 217–224.
Hallmayer J, Glasson EJ, Bower C, Petterson B, Croen L, Grether J et al. On the twin risk in autism. Am J Hum Genet 2002; 71: 941–946.
Hultman CM, Sparen P, Cnattingius S . Perinatal risk factors for infantile autism. Epidemiology 2002; 13: 417–423.
Le Couteur A, Bailey A, Goode S, Pickles A, Robertson S, Gottesman I et al. A broader phenotype of autism: the clinical spectrum in twins. J Child Psychol Psychiatry 1996; 37: 785–801.
Freitag C, IMGSAC. Phenotypic characteristics of siblings with autism and/or pervasive developmental disorder: evidence for heterogeneity. Am J Med Genet 2002; 114: 723.
Walker DR, Thompson A, Zwaigenbaum L, Goldberg J, Bryson SE, Mahoney WJ et al. Specifying PDD-NOS: a comparison of PDD-NOS, Asperger syndrome, and autism. J Am Acad Child Adolesc Psychiatry 2004; 43: 172–180.
Constantino JN, Todd RD . Genetic structure of reciprocal social behavior. Am J Psychiatry 2000; 157: 2043–2045.
Constantino JN, Hudziak JJ, Todd RD . Deficits in reciprocal social behavior in male twins: evidence for a genetically independent domain of psychopathology. J Am Acad Child Adolesc Psychiatry 2003; 42: 458–467.
Ronald A, Happe F, Plomin R . The genetic relationship between individual differences in social and nonsocial behaviours characteristic of autism. Dev Sci 2005; 8: 444–458.
Kolevzon A, Smith CJ, Schmeidler J, Buxbaum JD, Silverman JM . Familial symptom domains in monozygotic siblings with autism. Am J Med Genet B Neuropsychiatr Genet 2004; 129: 76–81.
Bolton P, Macdonald H, Pickles A, Rios P, Goode S, Crowson M et al. A case–control family history study of autism. J Child Psychol Psychiatry 1994; 35: 877–900.
Bishop DV, Maybery M, Wong D, Maley A, Hallmayer J . Characteristics of the broader phenotype in autism: a study of siblings using the children's communication checklist-2. Am J Med Genet B 2006; 141: 117–122.
Pilowsky T, Yirmiya N, Shalev RS, Gross-Tsur V . Language abilities of siblings of children with autism. J Child Psychol Psychiatry 2003; 44: 914–925.
Silverman JM, Smith CJ, Schmeidler J, Hollander E, Lawlor BA, Fitzgerald M et al. Symptom domains in autism and related conditions: evidence for familiality. Am J Med Genet 2002; 114: 64–73.
Pickles A, Starr E, Kazak S, Bolton P, Papanikolaou K, Bailey A et al. Variable expression of the autism broader phenotype: findings from extended pedigrees. J Child Psychol Psychiatry 2000; 41: 491–502.
MacLean JE, Szatmari P, Jones MB, Bryson SE, Mahoney WJ, Bartolucci G et al. Familial factors influence level of functioning in pervasive developmental disorder. J Am Acad Child Adolesc Psychiatry 1999; 38: 746–753.
Spiker D, Lotspeich L, Kraemer HC, Hallmayer J, McMahon W, Petersen PB et al. Genetics of autism: characteristics of affected and unaffected children from 37 multiplex families. Am J Med Genet 1994; 54: 27–35.
Folstein SE, Santangelo SL, Gilman SE, Piven J, Landa R, Lainhart J et al. Predictors of cognitive test patterns in autism families. J Child Psychol Psychiatry 1999; 40: 1117–1128.
Bailey A, Palferman S, Heavey L, Le Couteur A . Autism: the phenotype in relatives. J Autism Dev Disord 1998; 28: 369–392.
Bishop DV, Maybery M, Maley A, Wong D, Hill W, Hallmayer J . Using self-report to identify the broad phenotype in parents of children with autistic spectrum disorders: a study using the Autism-Spectrum Quotient. J Child Psychol Psychiatry 2004; 45: 1431–1436.
Ghaziuddin M . A family history study of Asperger syndrome. J Autism Dev Disord 2005; 35: 177–182.
Landa R, Folstein SE, Isaacs C . Spontaneous narrative-discourse performance of parents of autistic individuals. J Speech Hear Res 1991; 34: 1339–1345.
Landa R, Piven J, Wzorek MM, Gayle JO, Chase GA, Folstein SE . Social language use in parents of autistic individuals. Psychol Med 1992; 22: 245–254.
Piven J, Wzorek M, Landa R, Lainhart J, Bolton P, Chase GA et al. Personality characteristics of the parents of autistic individuals. Psychol Med 1994; 24: 783–795.
Piven J, Palmer P . Cognitive deficits in parents from multiple-incidence autism families. J Child Psychol Psychiatry 1997; 38: 1011–1021.
Szatmari P, MacLean JE, Jones MB, Bryson SE, Zwaigenbaum L, Bartolucci G et al. The familial aggregation of the lesser variant in biological and nonbiological relatives of PDD probands: a family history study. J Child Psychol Psychiatry 2000; 41: 579–586.
Wolff S, Narayan S, Moyes B . Personality characteristics of parents of autistic children: a controlled study. J Child Psychol Psychiatry 1988; 29: 143–153.
Lainhart JE, Ozonoff S, Coon H, Krasny L, Dinh E, Nice J et al. Autism, regression, and the broader autism phenotype. Am J Med Genet 2002; 113: 231–237.
Hollander E, King A, Delaney K, Smith CJ, Silverman JM . Obsessive-compulsive behaviors in parents of multiplex autism families. Psychiatry Res 2003; 117: 11–16.
Yirmiya N, Shaked M . Psychiatric disorders in parents of children with autism: a meta-analysis. J Child Psychol Psychiatry 2005; 46: 69–83.
Pickles A, Bolton P, Macdonald H, Bailey A, Le Couteur A, Sim CH et al. Latent-class analysis of recurrence risks for complex phenotypes with selection and measurement error: a twin and family history study of autism. Am J Hum Genet 1995; 57: 717–726.
Auranen M, Vanhala R, Varilo T, Ayers K, Kempas E, Ylisaukko-Oja T et al. A genomewide screen for autism-spectrum disorders: evidence for a major susceptibility locus on chromosome 3q25–27. Am J Hum Genet 2002; 71: 777–790.
Barrett S, Beck JC, Bernier R, Bisson E, Braun TA, Casavant TL et al. An autosomal genomic screen for autism. Collaborative linkage study of autism. Am J Med Genet 1999; 88: 609–615.
Bartlett CW, Goedken R, Vieland VJ . Effects of updating linkage evidence across subsets of data: reanalysis of the autism genetic resource exchange data set. Am J Hum Genet 2005; 76: 688–695.
Buxbaum JD, Silverman JM, Smith CJ, Kilifarski M, Reichert J, Hollander E et al. Evidence for a susceptibility gene for autism on chromosome 2 and for genetic heterogeneity. Am J Hum Genet 2001; 68: 1514–1520.
Cantor RM, Kono N, Duvall JA, Alvarez-Retuerto A, Stone JL, Alarcon M et al. Replication of autism linkage: fine-mapping peak at 17q21. Am J Hum Genet 2005; 76: 1050–1056.
Coon H, Matsunami N, Stevens J, Miller J, Pingree C, Camp NJ et al. Evidence for linkage on chromosome 3q25–27 in a large autism extended pedigree. Hum Hered 2005; 60: 220–226.
IMGSAC. A full genome screen for autism with evidence for linkage to a region on chromosome 7q. International Molecular Genetic Study of Autism Consortium. Hum Mol Genet 1998; 7: 571–578.
IMGSAC. A genomewide screen for autism: strong evidence for linkage to chromosomes 2q, 7q, and 16p. Am J Hum Genet 2001; 69: 570–581.
Lamb JA, Barnby G, Bonora E, Sykes N, Bacchelli E, Blasi F et al. Analysis of IMGSAC autism susceptibility loci: evidence for sex limited and parent of origin specific effects. J Med Genet 2005; 42: 132–137.
Lauritsen MB, Als TD, Dahl HA, Flint TJ, Wang AG, Vang M et al. A genome-wide search for alleles and haplotypes associated with autism and related pervasive developmental disorders on the Faroe Islands. Mol Psychiatry 2006; 11: 37–46.
Liu J, Nyholt DR, Magnussen P, Parano E, Pavone P, Geschwind D et al. A genomewide screen for autism susceptibility loci. Am J Hum Genet 2001; 69: 327–340.
McCauley JL, Li C, Jiang L, Olson LM, Crockett G, Gainer K et al. Genome-wide and Ordered-Subset linkage analyses provide support for autism loci on 17q and 19p with evidence of phenotypic and interlocus genetic correlates. BMC Med Genet 2005; 6: 1.
Philippe A, Martinez M, Guilloud-Bataille M, Gillberg C, Rastam M, Sponheim E et al. Genome-wide scan for autism susceptibility genes. Paris Autism Research International Sibpair Study. Hum Mol Genet 1999; 8: 805–812.
Risch N, Spiker D, Lotspeich L, Nouri N, Hinds D, Hallmayer J et al. A genomic screen of autism: evidence for a multilocus etiology. Am J Hum Genet 1999; 65: 493–507.
Shao Y, Wolpert CM, Raiford KL, Menold MM, Donnelly SL, Ravan SA et al. Genomic screen and follow-up analysis for autistic disorder. Am J Med Genet 2002; 114: 99–105.
Vincent JB, Melmer G, Bolton PF, Hodgkinson S, Holmes D, Curtis D et al. Genetic linkage analysis of the X chromosome in autism, with emphasis on the fragile X region. Psychiatr Genet 2005; 15: 83–90.
Yonan AL, Alarcon M, Cheng R, Magnusson PK, Spence SJ, Palmer AA et al. A genomewide screen of 345 families for autism-susceptibility loci. Am J Hum Genet 2003; 73: 886–897.
Ylisaukko-Oja T, Nieminen-von Wendt T, Kempas E, Sarenius S, Varilo T, von Wendt L et al. Genome-wide scan for loci of Asperger syndrome. Mol Psychiatry 2004; 9: 161–168.
Ylisaukko-Oja T, Alarcon M, Cantor RM, Auranen M, Vanhala R, Kempas E et al. Search for autism loci by combined analysis of Autism Genetic Resource Exchange and Finnish families. Ann Neurol 2006; 59: 145–155.
Alarcon M, Cantor RM, Liu J, Gilliam TC, Geschwind DH . Evidence for a language quantitative trait locus on chromosome 7q in multiplex autism families. Am J Hum Genet 2002; 70: 60–71.
Alarcon M, Yonan AL, Gilliam TC, Cantor RM, Geschwind DH . Quantitative genome scan and Ordered-Subsets Analysis of autism endophenotypes support language QTLs. Mol Psychiatry 2005; 10: 747–757.
Bradford Y, Haines J, Hutcheson H, Gardiner M, Braun T, Sheffield V et al. Incorporating language phenotypes strengthens evidence of linkage to autism. Am J Med Genet 2001; 105: 539–547.
Chen GK, Kono N, Geschwind DH, Cantor RM . Quantitative trait locus analysis of nonverbal communication in autism spectrum disorder. Mol Psychiatry 2006; 11: 214–220.
Shao Y, Raiford KL, Wolpert CM, Cope HA, Ravan SA, Ashley-Koch AA et al. Phenotypic homogeneity provides increased support for linkage on chromosome 2 in autistic disorder. Am J Hum Genet 2002; 70: 1058–1061.
Molloy CA, Keddache M, Martin LJ . Evidence for linkage on 21q and 7q in a subset of autism characterized by developmental regression. Mol Psychiatry 2005; 10: 741–746.
Buxbaum JD, Silverman J, Keddache M, Smith CJ, Hollander E, Ramoz N et al. Linkage analysis for autism in a subset families with obsessive-compulsive behaviors: evidence for an autism susceptibility gene on chromosome 1 and further support for susceptibility genes on chromosome 6 and 19. Mol Psychiatry 2004; 9: 144–150.
Ma DQ, Jaworski J, Menold MM, Donnelly S, Abramson RK, Wright HH et al. Ordered-subset analysis of savant skills in autism for 15q11–q13. Am J Med Genet B 2005; 135: 38–41.
Nurmi EL, Dowd M, Tadevosyan-Leyfer O, Haines JL, Folstein SE, Sutcliffe JS . Exploratory subsetting of autism families based on savant skills improves evidence of genetic linkage to 15q11–q13. J Am Acad Child Adolesc Psychiatry 2003; 42: 856–863.
Shao Y, Cuccaro ML, Hauser ER, Raiford KL, Menold MM, Wolpert CM et al. Fine mapping of autistic disorder to chromosome 15q11–q13 by use of phenotypic subtypes. Am J Hum Genet 2003; 72: 539–548.
Stone JL, Merriman B, Cantor RM, Yonan AL, Gilliam TC, Geschwind DH et al. Evidence for sex-specific risk alleles in autism spectrum disorder. Am J Hum Genet 2004; 75: 1117–1123.
Badner JA, Gershon ES . Regional meta-analysis of published data supports linkage of autism with markers on chromosome 7. Mol Psychiatry 2002; 7: 56–66.
Trikalinos TA, Karvouni A, Zintzaras E, Ylisaukko-Oja T, Peltonen L, Jarvela I et al. A heterogeneity-based genome search meta-analysis for autism-spectrum disorders. Mol Psychiatry 2006; 11: 29–36.
Yonan AL, Alarcon M, Cheng R, Magnusson PK, Spence SJ, Palmer AA et al. A genomewide screen of 345 families for autism-susceptibility loci. Am J Hum Genet 2003; 73: 886–897.
Hallmayer J, Spiker D, Lotspeich L, McMahon WM, Petersen PB, Nicholas P et al. Male-to-male transmission in extended pedigrees with multiple cases of autism. Am J Med Genet 1996; 67: 13–18.
Lander E, Kruglyak L . Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet 1995; 11: 241–247.
Nothnagel M, Rohde K . The effect of single-nucleotide polymorphism marker selection on patterns of haplotype blocks and haplotype frequency estimates. Am J Hum Genet 2005; 77: 988–998.
Bacchelli E, Blasi F, Biondolillo M, Lamb JA, Bonora E, Barnby G et al. Screening of nine candidate genes for autism on chromosome 2q reveals rare nonsynonymous variants in the cAMP–GEFII gene. Mol Psychiatry 2003; 8: 916–924.
Hamilton SP, Woo JM, Carlson EJ, Ghanem N, Ekker M, Rubenstein JL . Analysis of four DLX homeobox genes in autistic probands. BMC Genet 2005; 6: 52.
Rabionet R, Jaworski JM, Ashley-Koch AE, Martin ER, Sutcliffe JS, Haines JL et al. Analysis of the autism chromosome 2 linkage region: GAD1 and other candidate genes. Neurosci Lett 2004; 372: 209–214.
Segurado R, Conroy J, Meally E, Fitzgerald M, Gill M, Gallagher L . Confirmation of association between autism and the mitochondrial aspartate/glutamate carrier SLC25A12 gene on chromosome 2q31. Am J Psychiatry 2005; 162: 2182–2184.
Ramoz N, Reichert JG, Smith CJ, Silverman JM, Bespalova IN, Davis KL et al. Linkage and association of the mitochondrial aspartate/glutamate carrier SLC25A12 gene with autism. Am J Psychiatry 2004; 161: 662–669.
Blasi F, Bacchelli E, Carone S, Toma C, Monaco AP, Bailey AJ et al. SLC25A12 and CMYA3 gene variants are not associated with autism in the IMGSAC multiplex family sample. Eur J Hum Genet 2006; 14: 123–126.
Rabionet R, McCauley JL, Jaworski JM, Ashley-Koch AE, Martin ER, Sutcliffe JS et al. Lack of association between autism and SLC25A12. Am J Psychiatry 2006; 163: 929–931.
Jamain S, Betancur C, Quach H, Philippe A, Fellous M, Giros B et al. Linkage and association of the glutamate receptor 6 gene with autism. Mol Psychiatry 2002; 7: 302–310.
Shuang M, Liu J, Jia MX, Yang JZ, Wu SP, Gong XH et al. Family-based association study between autism and glutamate receptor 6 gene in Chinese Han trios. Am J Med Genet B 2004; 131: 48–50.
Watkins JC, Jane DE . The glutamate story. Br J Pharmacol 2006; 147(Suppl 1): S100–S108.
Purcell AE, Jeon OH, Zimmerman AW, Blue ME, Pevsner J . Postmortem brain abnormalities of the glutamate neurotransmitter system in autism. Neurology 2001; 57: 1618–1628.
Fisher SE, Vargha-Khadem F, Watkins KE, Monaco AP, Pembrey ME . Localisation of a gene implicated in a severe speech and language disorder. Nat Genet 1998; 18: 168–170.
Lai CS, Fisher SE, Hurst JA, Levy ER, Hodgson S, Fox M et al. The SPCH1 region on human 7q31: genomic characterization of the critical interval and localization of translocations associated with speech and language disorder. Am J Hum Genet 2000; 67: 357–368.
Gong X, Jia M, Ruan Y, Shuang M, Liu J, Wu S et al. Association between the FOXP2 gene and autistic disorder in Chinese population. Am J Med Genet B 2004; 127: 113–116.
Li H, Yamagata T, Mori M, Momoi MY . Absence of causative mutations and presence of autism-related allele in FOXP2 in Japanese autistic patients. Brain Dev 2005; 27: 207–210.
Gauthier J, Joober R, Mottron L, Laurent S, Fuchs M, De K et al. Mutation screening of FOXP2 in individuals diagnosed with autistic disorder. Am J Med Genet A 2003; 118: 172–175.
Marui T, Koishi S, Funatogawa I, Yamamoto K, Matsumoto H, Hashimoto O et al. No association of FOXP2 and PTPRZ1 on 7q31 with autism from the Japanese population. Neurosci Res 2005; 53: 91–94.
Newbury DF, Bonora E, Lamb JA, Fisher SE, Lai CS, Baird G et al. FOXP2 is not a major susceptibility gene for autism or specific language impairment. Am J Hum Genet 2002; 70: 1318–1327.
Wassink TH, Piven J, Vieland VJ, Pietila J, Goedken RJ, Folstein SE et al. Evaluation of FOXP2 as an autism susceptibility gene. Am J Med Genet 2002; 114: 566–569.
Fatemi SH, Snow AV, Stary JM, Araghi-Niknam M, Reutiman TJ, Lee S et al. Reelin signaling is impaired in autism. Biol Psychiatry 2005; 57: 777–787.
Fatemi SH, Stary JM, Egan EA . Reduced blood levels of reelin as a vulnerability factor in pathophysiology of autistic disorder. Cell Mol Neurobiol 2002; 22: 139–152.
Persico AM, D'Agruma L, Maiorano N, Totaro A, Militerni R, Bravaccio C et al. Reelin gene alleles and haplotypes as a factor predisposing to autistic disorder. Mol Psychiatry 2001; 6: 150–159.
Serajee FJ, Zhong H, Mahbubul Huq AH . Association of Reelin gene polymorphisms with autism. Genomics 2006; 87: 75–83.
Skaar DA, Shao Y, Haines JL, Stenger JE, Jaworski J, Martin ER et al. Analysis of the RELN gene as a genetic risk factor for autism. Mol Psychiatry 2005; 10: 563–571.
Bonora E, Beyer KS, Lamb JA, Parr JR, Klauck SM, Benner A et al. Analysis of reelin as a candidate gene for autism. Mol Psychiatry 2003; 8: 885–892.
Devlin B, Bennett P, Dawson G, Figlewicz DA, Grigorenko EL, McMahon W et al. Alleles of a reelin CGG repeat do not convey liability to autism in a sample from the CPEA network. Am J Med Genet B 2004; 126: 46–50.
Krebs MO, Betancur C, Leroy S, Bourdel MC, Gillberg C, Leboyer M . Absence of association between a polymorphic GGC repeat in the 5′ untranslated region of the reelin gene and autism. Mol Psychiatry 2002; 7: 801–804.
Li J, Nguyen L, Gleason C, Lotspeich L, Spiker D, Risch N et al. Lack of evidence for an association between WNT2 and RELN polymorphisms and autism. Am J Med Genet B 2004; 126: 51–57.
Zhang H, Liu X, Zhang C, Mundo E, Macciardi F, Grayson DR et al. Reelin gene alleles and susceptibility to autism spectrum disorders. Mol Psychiatry 2002; 7: 1012–1017.
Bonora E, Lamb JA, Barnby G, Sykes N, Moberly T, Beyer KS et al. Mutation screening and association analysis of six candidate genes for autism on chromosome 7q. Eur J Hum Genet 2005; 13: 198–207.
Hutcheson HB, Olson LM, Bradford Y, Folstein SE, Santangelo SL, Sutcliffe JS et al. Examination of NRCAM, LRRN3, KIAA0716, and LAMB1 as autism candidate genes. BMC Med Genet 2004; 5: 12.
Powell SK, Rao J, Roque E, Nomizu M, Kuratomi Y, Yamada Y et al. Neural cell response to multiple novel sites on laminin-1. J Neurosci Res 2000; 61: 302–312.
Persico AM, Bourgeron T . Searching for ways out of the autism maze: genetic, epigenetic and environmental clues. Trends Neurosci 2006; 29: 349–358.
Levy JB, Canoll PD, Silvennoinen O, Barnea G, Morse B, Honegger AM et al. The cloning of a receptor-type protein tyrosine phosphatase expressed in the central nervous system. J Biol Chem 1993; 268: 10573–10581.
Lijam N, Paylor R, McDonald MP, Crawley JN, Deng CX, Herrup K et al. Social interaction and sensorimotor gating abnormalities in mice lacking Dvl1. Cell 1997; 90: 895–905.
McCoy PA, Shao Y, Wolpert CM, Donnelly SL, Ashley-Koch A, Abel HL et al. No association between the WNT2 gene and autistic disorder. Am J Med Genet 2002; 114: 106–109.
Benayed R, Gharani N, Rossman I, Mancuso V, Lazar G, Kamdar S et al. Support for the homeobox transcription factor gene ENGRAILED 2 as an autism spectrum disorder susceptibility locus. Am J Hum Genet 2005; 77: 851–868.
Gharani N, Benayed R, Mancuso V, Brzustowicz LM, Millonig JH . Association of the homeobox transcription factor, ENGRAILED 2, 3, with autism spectrum disorder. Mol Psychiatry 2004; 9: 474–484.
Petit E, Herault J, Martineau J, Perrot A, Barthelemy C, Hameury L et al. Association study with two markers of a human homeogene in infantile autism. J Med Genet 1995; 32: 269–274.
Zhong H, Serajee FJ, Nabi R, Huq AH . No association between the EN2 gene and autistic disorder. J Med Genet 2003; 40: e4.
Bauman ML, Kemper TL . Neuroanatomic observations of the brain in autism: a review and future directions. Int J Dev Neurosci 2005; 23: 183–187.
Ingram JL, Stodgell CJ, Hyman SL, Figlewicz DA, Weitkamp LR, Rodier PM . Discovery of allelic variants of HOXA1 and HOXB1: genetic susceptibility to autism spectrum disorders. Teratology 2000; 62: 393–405.
Collins JS, Schroer RJ, Bird J, Michaelis RC . The HOXA1 A218G polymorphism and autism: lack of association in white and black patients from the South Carolina Autism Project. J Autism Dev Disord 2003; 33: 343–348.
Conciatori M, Stodgell CJ, Hyman SL, O'Bara M, Militerni R, Bravaccio C et al. Association between the HOXA1 A218G polymorphism and increased head circumference in patients with autism. Biol Psychiatry 2004; 55: 413–419.
Devlin B, Bennett P, Cook Jr EH, Dawson G, Gonen D, Grigorenko EL et al. No evidence for linkage of liability to autism to HOXA1 in a sample from the CPEA network. Am J Med Genet 2002; 114: 667–672.
Gallagher L, Hawi Z, Kearney G, Fitzgerald M, Gill M . No association between allelic variants of HOXA1/HOXB1 and autism. Am J Med Genet B 2004; 124: 64–67.
Li J, Tabor HK, Nguyen L, Gleason C, Lotspeich LJ, Spiker D et al. Lack of association between HoxA1 and HoxB1 gene variants and autism in 110 multiplex families. Am J Med Genet 2002; 114: 24–30.
Romano V, Cali F, Mirisola M, Gambino G, D' Anna R, Di Rosa P et al. Lack of association of HOXA1 and HOXB1 mutations and autism in Sicilian (Italian) patients. Mol Psychiatry 2003; 8: 716–717.
Talebizadeh Z, Bittel DC, Miles JH, Takahashi N, Wang CH, Kibiryeva N et al. No association between HOXA1 and HOXB1 genes and autism spectrum disorders (ASD). J Med Genet 2002; 39: e70.
Barrow JR, Stadler HS, Capecchi MR . Roles of Hoxa1 and Hoxa2 in patterning the early hindbrain of the mouse. Development 2000; 127: 933–944.
Lainhart JE, Piven J, Wzorek M, Landa R, Santangelo SL, Coon H et al. Macrocephaly in children and adults with autism. J Am Acad Child Adolesc Psychiatry 1997; 36: 282–290.
Fombonne E, Roge B, Claverie J, Courty S, Fremolle J . Microcephaly and macrocephaly in autism. J Autism Dev Disord 1999; 29: 113–119.
Rodier PM, Ingram JL, Tisdale B, Nelson S, Romano J . Embryological origin for autism: developmental anomalies of the cranial nerve motor nuclei. J Comp Neurol 1996; 370: 247–261.
Lainhart JE . Advances in autism neuroimaging research for the clinician and geneticist. Am J Med Genet C 2006; 142: 33–39.
Blatt GJ, Fitzgerald CM, Guptill JT, Booker AB, Kemper TL, Bauman ML . Density and distribution of hippocampal neurotransmitter receptors in autism: an autoradiographic study. J Autism Dev Disord 2001; 31: 537–543.
Hussman JP . Suppressed GABAergic inhibition as a common factor in suspected etiologies of autism. J Autism Dev Disord 2001; 31: 247–248.
Buxbaum JD, Silverman JM, Smith CJ, Greenberg DA, Kilifarski M, Reichert J et al. Association between a GABRB3 polymorphism and autism. Mol Psychiatry 2002; 7: 311–316.
Cook Jr EH, Courchesne RY, Cox NJ, Lord C, Gonen D, Guter SJ et al. Linkage-disequilibrium mapping of autistic disorder, with 15q11–13 markers. Am J Hum Genet 1998; 62: 1077–1083.
Curran S, Roberts S, Thomas S, Veltman M, Browne J, Medda E et al. An association analysis of microsatellite markers across the Prader–Willi/Angelman critical region on chromosome 15 (q11–13) and autism spectrum disorder. Am J Med Genet B 2005; 137: 25–28.
Maestrini E, Lai C, Marlow A, Matthews N, Wallace S, Bailey A et al. Serotonin transporter (5-HTT) and gamma-aminobutyric acid receptor subunit beta3 (GABRB3) gene polymorphisms are not associated with autism in the IMGSA families. The International Molecular Genetic Study of Autism Consortium. Am J Med Genet 1999; 88: 492–496.
Martin ER, Menold MM, Wolpert CM, Bass MP, Donnelly SL, Ravan SA et al. Analysis of linkage disequilibrium in gamma-aminobutyric acid receptor subunit genes in autistic disorder. Am J Med Genet 2000; 96: 43–48.
Salmon B, Hallmayer J, Rogers T, Kalaydjieva L, Petersen PB, Nicholas P et al. Absence of linkage and linkage disequilibrium to chromosome 15q11–q13 markers in 139 multiplex families with autism. Am J Med Genet 1999; 88: 551–556.
McCauley JL, Olson LM, Delahanty R, Amin T, Nurmi EL, Organ EL et al. A linkage disequilibrium map of the 1-Mb 15q12 GABA(A) receptor subunit cluster and association to autism. Am J Med Genet B 2004; 131: 51–59.
Menold MM, Shao Y, Wolpert CM, Donnelly SL, Raiford KL, Martin ER et al. Association analysis of chromosome 15 gabaa receptor subunit genes in autistic disorder. J Neurogenet 2001; 15: 245–259.
Ashley-Koch AE, Mei H, Jaworski J, Ma DQ, Ritchie MD, Menold MM et al. An analysis paradigm for investigating multi-locus effects in complex disease: examination of three GABA receptor subunit genes on 15q11–q13 as risk factors for autistic disorder. Ann Hum Genet 2006; 70: 281–292.
Ma DQ, Whitehead PL, Menold MM, Martin ER, Ashley-Koch AE, Mei H et al. Identification of significant association and gene–gene interaction of GABA receptor subunit genes in autism. Am J Hum Genet 2005; 77: 377–388.
Kim SJ, Herzing LB, Veenstra-VanderWeele J, Lord C, Courchesne R, Leventhal BL et al. Mutation screening and transmission disequilibrium study of ATP10C in autism. Am J Med Genet 2002; 114: 137–143.
Nurmi EL, Amin T, Olson LM, Jacobs MM, McCauley JL, Lam AY et al. Dense linkage disequilibrium mapping in the 15q11–q13 maternal expression domain yields evidence for association in autism. Mol Psychiatry 2003; 8: 624–634, 570.
Nurmi EL, Bradford Y, Chen Y, Hall J, Arnone B, Gardiner MB et al. Linkage disequilibrium at the Angelman syndrome gene UBE3A in autism families. Genomics 2001; 77: 105–113.
Anderson GM, Freedman DX, Cohen DJ, Volkmar FR, Hoder EL, McPhedran P et al. Whole blood serotonin in autistic and normal subjects. J Child Psychol Psychiatry 1987; 28: 885–900.
Abramson RK, Wright HH, Carpenter R, Brennan W, Lumpuy O, Cole E et al. Elevated blood serotonin in autistic probands and their first-degree relatives. J Autism Dev Disord 1989; 19: 397–407.
Leboyer M, Philippe A, Bouvard M, Guilloud-Bataille M, Bondoux D, Tabuteau F et al. Whole blood serotonin and plasma beta-endorphin in autistic probands and their first-degree relatives. Biol Psychiatry 1999; 45: 158–163.
Lesch KP, Balling U, Gross J, Strauss K, Wolozin BL, Murphy DL et al. Organization of the human serotonin transporter gene. J Neural Transm Gen Sect 1994; 95: 157–162.
Heils A, Teufel A, Petri S, Stober G, Riederer P, Bengel D et al. Allelic variation of human serotonin transporter gene expression. J Neurochem 1996; 66: 2621–2624.
Greenberg BD, Tolliver TJ, Huang SJ, Li Q, Bengel D, Murphy DL . Genetic variation in the serotonin transporter promoter region affects serotonin uptake in human blood platelets. Am J Med Genet 1999; 88: 83–87.
Cook Jr EH, Courchesne R, Lord C, Cox NJ, Yan S, Lincoln A et al. Evidence of linkage between the serotonin transporter and autistic disorder. Mol Psychiatry 1997; 2: 247–250.
Devlin B, Cook Jr EH, Coon H, Dawson G, Grigorenko EL, McMahon W et al. Autism and the serotonin transporter: the long and short of it. Mol Psychiatry 2005; 10: 1110–1116.
Kim SJ, Cox N, Courchesne R, Lord C, Corsello C, Akshoomoff N et al. Transmission disequilibrium mapping at the serotonin transporter gene (SLC6A4) region in autistic disorder. Mol Psychiatry 2002; 7: 278–288.
Sutcliffe JS, Delahanty RJ, Prasad HC, McCauley JL, Han Q, Jiang L et al. Allelic heterogeneity at the serotonin transporter locus (SLC6A4) confers susceptibility to autism and rigid-compulsive behaviors. Am J Hum Genet 2005; 77: 265–279.
Klauck SM, Poustka F, Benner A, Lesch KP, Poustka A . Serotonin transporter (5-HTT) gene variants associated with autism? Hum Mol Genet 1997; 6: 2233–2238.
Yirmiya N, Pilowsky T, Nemanov L, Arbelle S, Feinsilver T, Fried I et al. Evidence for an association with the serotonin transporter promoter region polymorphism and autism. Am J Med Genet 2001; 105: 381–386.
Betancur C, Corbex M, Spielewoy C, Philippe A, Laplanche JL, Launay JM et al. Serotonin transporter gene polymorphisms and hyperserotonemia in autistic disorder. Mol Psychiatry 2002; 7: 67–71.
Coutinho AM, Oliveira G, Morgadinho T, Fesel C, Macedo TR, Bento C et al. Variants of the serotonin transporter gene (SLC6A4) significantly contribute to hyperserotonemia in autism. Mol Psychiatry 2004; 9: 264–271.
Koishi S, Yamamoto K, Matsumoto H, Koishi S, Enseki Y, Oya A et al. Serotonin transporter gene promoter polymorphism and autism: a family-based genetic association study in Japanese population. Brain Dev 2006; 28: 257–260.
Mulder EJ, Anderson GM, Kema IP, Brugman AM, Ketelaars CE, de Bildt A et al. Serotonin transporter intron 2 polymorphism associated with rigid-compulsive behaviors in Dutch individuals with pervasive developmental disorder. Am J Med Genet B 2005; 133: 93–96.
Persico AM, Militerni R, Bravaccio C, Schneider C, Melmed R, Conciatori M et al. Lack of association between serotonin transporter gene promoter variants and autistic disorder in two ethnically distinct samples. Am J Med Genet 2000; 96: 123–127.
Tordjman S, Gutknecht L, Carlier M, Spitz E, Antoine C, Slama F et al. Role of the serotonin transporter gene in the behavioral expression of autism. Mol Psychiatry 2001; 6: 434–439.
Wu S, Guo Y, Jia M, Ruan Y, Shuang M, Liu J et al. Lack of evidence for association between the serotonin transporter gene (SLC6A4) polymorphisms and autism in the Chinese trios. Neurosci Lett 2005; 381: 1–5.
Zhong N, Ye L, Ju W, Brown WT, Tsiouris J, Cohen I . 5-HTTLPR variants not associated with autistic spectrum disorders. Neurogenetics 1999; 2: 129–131.
Anderson GM, Gutknecht L, Cohen DJ, Brailly-Tabard S, Cohen JH, Ferrari P et al. Serotonin transporter promoter variants in autism: functional effects and relationship to platelet hyperserotonemia. Mol Psychiatry 2002; 7: 831–836.
Persico AM, Pascucci T, Puglisi-Allegra S, Militerni R, Bravaccio C, Schneider C et al. Serotonin transporter gene promoter variants do not explain the hyperserotonemia in autistic children. Mol Psychiatry 2002; 7: 795–800.
Conroy J, Meally E, Kearney G, Fitzgerald M, Gill M, Gallagher L . Serotonin transporter gene and autism: a haplotype analysis in an Irish autistic population. Mol Psychiatry 2004; 9: 587–593.
Blasi F, Bacchelli E, Pesaresi G, Carone S, Bailey AJ, Maestrini E . Absence of coding mutations in the X-linked genes neuroligin 3 and neuroligin 4 in individuals with autism from the IMGSAC collection. Am J Med Genet B Neuropsychiatr Genet 2006; 141: 220–221.
Jamain S, Quach H, Betancur C, Rastam M, Colineaux C, Gillberg IC et al. Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nat Genet 2003; 34: 27–29.
Laumonnier F, Bonnet-Brilhault F, Gomot M, Blanc R, David A, Moizard MP et al. X-linked mental retardation and autism are associated with a mutation in the NLGN4 gene, a member of the neuroligin family. Am J Hum Genet 2004; 74: 552–557.
Yan J, Oliveira G, Coutinho A, Yang C, Feng J, Katz C et al. Analysis of the neuroligin 3 and 4 genes in autism and other neuropsychiatric patients. Mol Psychiatry 2005; 10: 329–332.
Gauthier J, Bonnel A, St Onge J, Karemera L, Laurent S, Mottron L et al. NLGN3/NLGN4 gene mutations are not responsible for autism in the Quebec population. Am J Med Genet B 2005; 132: 74–75.
Talebizadeh Z, Bittel DC, Veatch OJ, Butler MG, Takahashi TN, Miles JH . Do known mutations in neuroligin genes (NLGN3 and NLGN4) cause autism? J Autism Dev Disord 2004; 34: 735–736.
Vincent JB, Kolozsvari D, Roberts WS, Bolton PF, Gurling HM, Scherer SW . Mutation screening of X-chromosomal neuroligin genes: no mutations in 196 autism probands. Am J Med Genet B 2004; 129: 82–84.
Ylisaukko-Oja T, Rehnstrom K, Auranen M, Vanhala R, Alen R, Kempas E et al. Analysis of four neuroligin genes as candidates for autism. Eur J Hum Genet 2005; 13: 1285–1292.
Beyer KS, Blasi F, Bacchelli E, Klauck SM, Maestrini E, Poustka A . Mutation analysis of the coding sequence of the MECP2 gene in infantile autism. Hum Genet 2002; 111: 305–309.
Carney RM, Wolpert CM, Ravan SA, Shahbazian M, Ashley-Koch A, Cuccaro ML et al. Identification of MeCP2 mutations in a series of females with autistic disorder. Pediatr Neurol 2003; 28: 205–211.
Lam CW, Yeung WL, Ko CH, Poon PM, Tong SF, Chan KY et al. Spectrum of mutations in the MECP2 gene in patients with infantile autism and Rett syndrome. J Med Genet 2000; 37: E41.
Li H, Yamagata T, Mori M, Yasuhara A, Momoi MY . Mutation analysis of methyl-CpG binding protein family genes in autistic patients. Brain Dev 2005; 27: 321–325.
Lobo-Menendez F, Sossey-Alaoui K, Bell JM, Copeland-Yates SA, Plank SM, Sanford SO et al. Absence of MeCP2 mutations in patients from the South Carolina autism project. Am J Med Genet B 2003; 117: 97–101.
Shibayama A, Cook Jr EH, Feng J, Glanzmann C, Yan J, Craddock N et al. MECP2 structural and 3′-UTR variants in schizophrenia, autism and other psychiatric diseases: a possible association with autism. Am J Med Genet B 2004; 128: 50–53.
van Karnebeek CD, van GI, Nijhof GJ, Abeling NG, Vreken P, Redeker EJ et al. An aetiological study of 25 mentally retarded adults with autism. J Med Genet 2002; 39: 205–213.
Zappella M, Meloni I, Longo I, Canitano R, Hayek G, Rosaia L et al. Study of MECP2 gene in Rett syndrome variants and autistic girls. Am J Med Genet B 2003; 119: 102–107.
Cohen IL, Liu X, Schutz C, White BN, Jenkins EC, Brown WT et al. Association of autism severity with a monoamine oxidase A functional polymorphism. Clin Genet 2003; 64: 190–197.
Philippe A, Guilloud-Bataille M, Martinez M, Gillberg C, Rastam M, Sponheim E et al. Analysis of ten candidate genes in autism by association and linkage. Am J Med Genet 2002; 114: 125–128.
Yirmiya N, Pilowsky T, Tidhar S, Nemanov L, Altmark L, Ebstein RP . Family-based and population study of a functional promoter-region monoamine oxidase A polymorphism in autism: possible association with IQ. Am J Med Genet 2002; 114: 284–287.
Simonoff E . Genetic counseling in autism and pervasive developmental disorders. J Autism Dev Disord 1998; 28: 447–456.
McMahon WM, Baty BJ, Botkin J . Genetic counseling and ethical issues for autism. Am J Med Genet C 2006; 142: 52–57.
Gschwind DH, Sowinski J, Lord C, Iversen P, Shestack J, Jones P et al. The autism genetic resource exchange: a resource for the study of autism and related neuropsychiatric conditions. Am J Hum Genet 2001; 69: 463–466.
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Freitag, C. The genetics of autistic disorders and its clinical relevance: a review of the literature. Mol Psychiatry 12, 2–22 (2007). https://doi.org/10.1038/sj.mp.4001896
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