XLMR genes: update 2000

Abstract

This is the sixth edition of the catalogue of XLMR genes, ie X-linked genes whose malfunctioning causes mental retardation. The cloning era is not yet concluded, actually much remains to be done to account for the 202 XLMR conditions listed in this update. Many of these may eventually prove to be due to mutations in the same gene but the present number of 33 cloned genes falls surely short of the actual total count. It is now clear that even small families or individual patients with cytogenetic rearrangements can be instrumental in pinning down the remaining genes. DNA chip technology will hopefully allow (re)screening large numbers of patients for mutations in candidate genes or testing the expression levels of many candidate genes in informative families. Slowly, our knowledge of the structure and functioning of the proteins encoded by these genes is beginning to cast some light on the biological pathways required for the normal development of intelligence. Correlations between the molecular defects and the phenotypic manifestations are also being established. In order to facilitate the exchange of existing information and to allow its timely update, we prepared the first edition of the XLMR database (available at http://homepages.go.com/xlmr/home.htm) and invite all colleagues, expert in the field, to contribute with their experience.

References

  1. 1

    Chiurazzi P, Oostra BA: . Genetics of mental retardation. Curr Opin Pediat 2000 12: 529–535.

    CAS  Google Scholar 

  2. 2

    Lehrke R: . Theory of X-linkage of major intellectual traits. Am J Ment Defic 1972 76: 611–619.

    CAS  PubMed  Google Scholar 

  3. 3

    Turner G, Turner B: . X-linked mental retardation. J Med Genet 1974 11: 109–113.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. 4

    Neri G, Chiurazzi P: . X-linked mental retardation. Adv Genet 1999 41: 55–94.

    CAS  PubMed  Google Scholar 

  5. 5

    Herbst DS, Miller JR: . Nonspecific X-linked mental retardation II: the frequency in British Columbia. Am J Med Genet 1980 7: 461–469.

    CAS  PubMed  Google Scholar 

  6. 6

    Turner G, Webb T, Wake S, Robinson H: . Prevalence of fragile X syndrome. Am J Med Genet 1996 64: 196–197.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. 7

    Neri G, Gurrieri F, Gal A, Lubs HA: . XLMR genes: update 1990. Am J Med Genet 1991 38: 186–189.

    CAS  PubMed  Google Scholar 

  8. 8

    Lubs H, Chiurazzi P, Arena J, Schwartz C, Tranebjaerg L, Neri G: . XLMR genes: update 1998. Am J Med Genet 1999 83: 237–247.

    CAS  PubMed  Google Scholar 

  9. 9

    Hamel B, Chiurazzi P, Lubs H: . Syndromic XLMR genes (MRXS): update 2000. Am J Med Genet 2000 94: 361–366.

    CAS  PubMed  Google Scholar 

  10. 10

    Chelly J: . Breakthroughs in molecular and cellular mechanisms underlying X-linked mental retardation. Hum Mol Genet 1999 8: 1833–1838.

    CAS  PubMed  Google Scholar 

  11. 11

    Toniolo D, D'Adamo P: . X-linked non-specific mental retardation. Curr Opin Genet Dev 2000 10: 280–285.

    CAS  PubMed  Google Scholar 

  12. 12

    Merienne K, Jacquot S, Pannetier S et al:. A missense mutation in RPS6KA3 (RSK2) responsible for non-specific mental retardation. Nat Genet 1999 22: 13–14.

    CAS  PubMed  Google Scholar 

  13. 13

    Orrico A, Lam CW, Galli L et al. . MeCP2 mutation in male patients with non-specific X-linked mental retardation. FEBS Lett 2000 24106: 1–4.

    Google Scholar 

  14. 14

    Brzustowicz LM, Farrell S, Khan MB, Weksberg R: . Mapping of a new SGBS locus to chromosome Xp22 in a family with a severe form of Simpson-Golabi-Behmel syndrome. Am J Hum Genet 1999 65: 779–783.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. 15

    Abidi F, Schwartz CE, Carpenter NJ, Villard L, Fontes M, Curtis M: . Carpenter-Waziri syndrome results from a mutation in XNP. Am J Med Genet 1999 85: 249–251.

    CAS  PubMed  Google Scholar 

  16. 16

    Schwartz C, Abidi A, Lubs H, Stevenson R: . A mutation inXNP results in the Holmes-Gang syndrome: further evidence that mutations in XNP may account for a relatively large fraction of mental retardation in males. Eur J Hum Genet 1999 7: (S1) 37.

    Google Scholar 

  17. 17

    Lossi AM, Millan JM, Villard L et al:. Mutation of the XNP/ATR-X gene in a family with severe mental retardation, spastic paraplegia and skewed pattern of X inactivation: demonstration that the mutation is involved in the inactivation bias. Am J Hum Genet 1999 65: 558–562.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. 18

    Villard L, Fontes M, Ades LC, Gecz J: . Identification of a mutation in the XNP/ATR-X gene in a family reported as Smith-Fineman-Myers syndrome. Am J Med Genet 2000 91: 83–85.

    CAS  PubMed  Google Scholar 

  19. 19

    Zollino M, Mastroiacovo P, Zampino G, Mariotti P, Neri G: . A new XLMR syndrome with characteristic face, hypogenitalism, congenital hypotonia and pachygyria. Am J Med Genet 1992 43: 452–457.

    CAS  PubMed  Google Scholar 

  20. 20

    Antonarakis SE, Van Aelst L: . Mind the GAP, Rho, Rab and GDI. Nat Genet 1998 19: 106–108.

    CAS  PubMed  Google Scholar 

  21. 21

    Siber M: . X-linked recessive microencephaly, microphthalmia with corneal opacities, spastic quadriplegia, hypospadias and cryptorchidism. Clin Genet 1984 26: 453–456.

    CAS  PubMed  Google Scholar 

  22. 22

    Abidi F, Hall BD, Cadle RG et al:. X-linked mental retardation with variable stature, head circumference, and testicular volume linked to Xq12-q21. Am J Med Genet 1999 85: 223–229.

    CAS  PubMed  Google Scholar 

  23. 23

    Ahmad W, De Fusco M, ul Haque MF et al:. Linkage mapping of a new syndromic form of X-linked mental retardation, MRXS7, associated with obesity. Eur J Hum Genet 1999 7: 828–832.

    CAS  PubMed  Google Scholar 

  24. 24

    Aldred MA, Dry KL, Knight-Jones EB et al:. Genetic analysis of a kindred with X-linked mental handicap and retinitis pigmentosa. Am J Hum Genet 1994 55: 916–922.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. 25

    Armfield K, Nelson R, Lubs HA et al:. X-linked mental retardation syndrome with short stature, small hands and feet, seizures, cleft palate, and glaucoma is linked to Xq28. Am J Med Genet 1999 85: 236–242.

    CAS  PubMed  Google Scholar 

  26. 26

    Atkin JF, Flaitz K, Patil S, Smith W: . A new X-linked mental retardation syndrome. Am J Med Genet 1985 21: 697–705.

    CAS  PubMed  Google Scholar 

  27. 27

    Baraitser M, Reardon W, Vijeratnam S: . Nonspecific X-linked mental retardation with macrocephaly and obesity: a further family. Am J Med Genet 1995 57: 380–384.

    CAS  PubMed  Google Scholar 

  28. 28

    Carpenter NJ, Givens H, Randell L, Lutz R, Miles JH: . Clinical characterization and gene mapping of a family with X-linked mental retardation, facial dysmorphism, congenital hip dislocation and skewed pattern of X-inactivation. Am J Hum Genet 2000 67: (Suppl.2) 315.

    Google Scholar 

  29. 29

    Chudley AE, Tackels DC, Lubs HA et al:. X-linked mental retardation syndrome with seizures, hypogammaglobulinemia, and progressive gait disturbance is regionally mapped between xq21.33 and Xq23. Am J Med Genet 1999 85: 255–262.

    CAS  PubMed  Google Scholar 

  30. 30

    Golabi M, Ito M, Hall BD: . A new X-linked multiple congenital anomalies/mental retardation syndrome. Am J Med Genet 1984 17: 367–374.

    CAS  PubMed  Google Scholar 

  31. 31

    Hall BD, Robl JM: . New X-linked MR/MCA syndrome associated with cleft lip/palate, upslanted/short palpebral fissures, high nasal bridge, prominent nasal tip, inguinal hernia and minor digital defects. Am J Hum Genet 1999 65: A151.

    Google Scholar 

  32. 32

    Hamel BC, Mariman EC, van Beersum SE, Schoonbrood-Lenssen AM, Ropers HH: . Mental retardation, congenital heart defect, cleft palate, short stature, and facial anomalies: a new X-linked multiple congenital anomalies/mental retardation syndrome: clinical description and molecular studies. Am J Med Genet 1994 51: 591–597.

    CAS  PubMed  Google Scholar 

  33. 33

    Hockey A: . X-linked intellectual handicap and precocious puberty with obesity in carrier females. Am J Med Genet 1986 23: 127–137.

    CAS  PubMed  Google Scholar 

  34. 34

    Homfray T, Holland T, Patton M: . A new X-linked mental retardation syndrome. Clin Dysmorphol 1995 4: 289–293.

    CAS  PubMed  Google Scholar 

  35. 35

    Johnson JP, Nelson R, Schwartz CE: . A family with mental retardation, variable macrocephaly and macro-orchidism, and linkage to Xq12-q21. J Med Genet 1998 35: 1026–1030.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. 36

    Kang WM, Huang CC, Lin SJ: . X-linked recessive inheritance of dysgenesis of corpus callosum in a Chinese family. Am J Med Genet 1992 44: 619–623.

    CAS  PubMed  Google Scholar 

  37. 37

    Lubs H, Abidi F, Bier JA et al. . XLMR syndrome characterized by multiple respiratory infections, hypertelorism, severe CNS deterioration and early death localizes to distal Xq28. Am J Med Genet 1999 85: 243–248.

    CAS  PubMed  Google Scholar 

  38. 38

    Steinmuller R, Steinberger D, Muller U: . MEHMO (mental retardation, epileptic seizures, hypogonadism and -genitalism, microcephaly, obesity), a novel syndrome: assignmentof disease locus to xp21.1-p22.13. Eur J Hum Genet 1998 6: 201–206.

    CAS  PubMed  Google Scholar 

  39. 39

    Oosterwijk JC, Wischmeijer A, Losekoot M, Haraldson A, Theunissen G, van Gelderen I: . A new X-linked mental retardation syndrome with distal limb defects, hearing impairment, verrucosis and immunodeficiency. Am J Hum Genet 1999 65: A337.

    Google Scholar 

  40. 40

    Porteous MEM, Johnson H, Burn J et al:. A new mental retardation syndrome mapping to the pericentrometric region of the X chromosome. Am J Hum Genet 1992 51: A106.

    Google Scholar 

  41. 41

    Reish O, Gorlin RJ, Hordinsky M, Rest EB, Burke B, Berry SA: . Brain anomalies, retardation of mentality and growth, ectodermal dysplasia, skeletal malformations, Hirschsprung disease, ear deformity and deafness, eye hypoplasia, cleft palate, cryptorchidism, and kidney dysplasia/hypoplasia (BRESEK/BRESHECK): new X-linked syndrome? Am J Med Genet 1997 68: 386–390.

    CAS  PubMed  Google Scholar 

  42. 42

    Seemanova E, Lesny I: . X-linked microcephaly, microphthalmia, microcornea, congenital cataract, hypogenitalism, mental deficiency, growth retardation, spasticity: possible new syndrome. Am J Med Genet 1996 66: 179–183.

    CAS  PubMed  Google Scholar 

  43. 43

    Shashi V, Berry MN, Shoaf S, Sciote JJ, Goldstein D, Hart TC: . A unique form of mental retardation with a distinctive phenotype maps to Xq26-q27. Am J Hum Genet 2000 66: 469–479.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. 44

    Shrimpton AE, Daly KM, Hoo JJ: . Mapping of a gene (MRXS9) for X-linked mental retardation, microcephaly, and variably short stature to Xq12-q21.31. Am J Med Genet 1999 84: 293–299.

    CAS  PubMed  Google Scholar 

  45. 45

    Siderius LE, Hamel BC, van Bokhoven H et al:. X-linked mental retardation associated with cleft lip/palate maps to Xp11.3-q21.3. Am J Med Genet 1999 85: 216–220.

    CAS  PubMed  Google Scholar 

  46. 46

    Brooks SS, Wisniewski K, Brown WT: . New X-linked mental retardation (XLMR) syndrome with distinct facial appearance and growth retardation. Am J Med Genet 1994 51: 586–590.

    CAS  PubMed  Google Scholar 

  47. 47

    Stevenson RE, Hane B, Arena JF et al:. Arch fingerprints, hypotonia, and areflexia associated with X linked mental retardation. J Med Genet 1997 34: 465–469.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. 48

    dos Santos RC, Barretto OC, Nonoyama K et al. . X-linked syndrome: mental retardation, hip luxation, and G6PD variant. Am J Med Genet 1991 39: 133–136.

    CAS  PubMed  Google Scholar 

  49. 49

    Stoll C, Geraudel A, Chauvin A: . New X-linked syndrome of mental retardation, short stature, and hypertelorism. Am J Med Genet 1991 39: 474–478.

    CAS  PubMed  Google Scholar 

  50. 50

    Tariverdian G, Froster-Iskenius U, Deuschl G, Wolff G: . Mental retardation, acromegalic face, and megalotestes in two half-brothers: a specific form of X-linked mental retardation without fra(X)(q)? Am J Med Genet 1991 38: 208–211.

    CAS  PubMed  Google Scholar 

  51. 51

    Turner G, Gedeon A, Mulley J: . X-linked mental retardation with heterozygous expression and macrocephaly: pericentromeric gene localization. Am J Med Genet 1994 51: 575–580.

    CAS  PubMed  Google Scholar 

  52. 52

    Vasquez SB, Hurst DL, Sotos JF: . X-linked hypogonadism, gynecomastia, mental retardation, short stature, and obesity–a new syndrome. J Pediatr 1979 94: 56–60.

    CAS  PubMed  Google Scholar 

  53. 53

    Vitale E, Specchia C, Devoto M et al:. A novel X-linked mental retardation syndrome with short stature maps to Xq24. Am J Hum Genet 2000 67: (Suppl.2) 332.

    Google Scholar 

  54. 54

    Vles JS, Fryns JP, Folmer K et al:. Corpus callosum agenesis, spastic quadriparesis and irregular lining of the lateral ventricles on CT-scan. A distinct X-linked mental retardation syndrome? Genet Couns 1990 1: 97–102.

    CAS  PubMed  Google Scholar 

  55. 55

    Wittwer B, Kircheisen R, Leutelt J, Orth U, Gal A: . New X-linked mental retardation syndrome with the gene mapped tentatively in Xp22.3. Am J Med Genet 1996 64: 42–49.

    CAS  PubMed  Google Scholar 

  56. 56

    Young ID, Hughes HE: . Sex-linked mental retardation, short stature, obesity and hypogonadism: report of a family. J Ment Defic Res 1982 26: 153–162.

    CAS  PubMed  Google Scholar 

  57. 57

    Arena JF, Schwartz C, Stevenson R et al. . Spastic paraplegia with iron deposits in the basal ganglia: a new X-linked mental retardation syndrome. Am J Med Genet 1992 43: 479–490.

    CAS  PubMed  Google Scholar 

  58. 58

    Dobyns WB, Berry-Kravis E, Havernick NJ, Holden KR, Viskochil D: . X-linked lissencephaly with absent corpus callosum and ambiguous genitalia. Am J Med Genet 1999 86: 331–337.

    CAS  PubMed  Google Scholar 

  59. 59

    des Portes V, Bachner L, Bruls T et al:. X-linked neurodegenerative syndrome with congenital ataxia, late-onset progressive myoclonic encephalopathy and selective macular degeneration, linked to Xp22.33-pter. Am J Med Genet 1996 64: 69–72.

    CAS  PubMed  Google Scholar 

  60. 60

    Cabezas DA, Slaugh R, Abidi F et al:. A new X linked mental retardation (XLMR) syndrome with short stature, small testes, muscle wasting, and tremor localises to Xq24-q25. J Med Genet 1997 37: 663–668.

    Google Scholar 

  61. 61

    Claes S, Devriendt K, Van Goethem G et al:. Novel syndromic form of X-linked complicated spastic paraplegia. Am J Med Genet 94: 1–4.

  62. 62

    Strain L, Wright AF, Bonthron DT: . Fried syndrome is a distinct X linked mental retardation syndrome mapping to Xp22. J Med Genet 1997 34: 535–540.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. 63

    Garcia CC, Buddles MRH, Seager M, Goodship JA: . A family with X-linked epilepsy mapping to Xp11-Xq13. Am J Hum Genet 1999 65: A250.

    Google Scholar 

  64. 64

    Hamel BC, Wesseling P, Renier WO et al:. A new X linked neurodegenerative syndrome with mental retardation, blindness, convulsions, spasticity, mild hypomyelination, and early death maps to the pericentromeric region. J Med Genet 1999 36: 140–143.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. 65

    Steinmuller R, Lantigua-Cruz A, Garcia-Garcia R, Kostrzewa M, Steinberger D, Muller U: . Evidence of a third locus in X-linked recessive spastic paraplegia. Hum Genet 1997 100: 287–289.

    CAS  PubMed  Google Scholar 

  66. 66

    Tranebjaerg L, Lou H, Andresen J: . New X-linked syndrome with apraxia, ataxia, and mental deficiency: clinical, cytogenetic and neuropsychological studies in two Danish families. Am J Med Genet 1992 43: 498–504.

    CAS  PubMed  Google Scholar 

  67. 67

    Hedera P, Alvarado D, Beydoun A, Fink JK: . Novel mental retardation-epilepsy syndrome linked to Xp21.1-p11.4. Am J Hum Genet 2000 67: (Suppl.2) 332.

    Google Scholar 

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Acknowledgements

The authors are greatly indebted to the many colleagues and fellow scientists all over the world who have brought to our attention items to be included or excluded, additional references and other relevant information.

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Correspondence to Giovanni Neri.

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Chiurazzi, P., Hamel, B. & Neri, G. XLMR genes: update 2000. Eur J Hum Genet 9, 71–81 (2001). https://doi.org/10.1038/sj.ejhg.5200603

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Keywords

  • mental retardation
  • X chromosome
  • XLMR
  • MRXS
  • MRX
  • on-line database

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