Nature Genetics
31, 435 - 438 (2002)
Published online: 15 July 2002; | doi:10.1038/ng935
Identification of the gene (BBS1) most commonly involved in Bardet-Biedl syndrome, a complex human obesity syndromeKirk Mykytyn1, Darryl Y. Nishimura1, Charles C. Searby1, Mythreyi Shastri1, Hsan-jan Yen1, John S. Beck1, Terry Braun2, Luan M. Streb3, Alberto S. Cornier4, Gerald F. Cox5, Anne B. Fulton6, Rivka Carmi7, Güven Lüleci8, Settara C. Chandrasekharappa9, Francis S. Collins9, Samuel G. Jacobson10, John R. Heckenlively11, Richard G. Weleber12, Edwin M. Stone3
& Val C. Sheffield11
Department of Pediatrics, Division of Medical Genetics and the Howard Hughes Medical Institute, University of Iowa, Iowa City, Iowa 52242, USA. 2
Department of Electrical Engineering, University of Iowa, Iowa City, Iowa 52242, USA. 3
Department of Ophthalmology, University of Iowa, Iowa City, Iowa 52242, USA. 4
Department of Biochemistry, Ponce School of Medicine, Ponce, Puerto Rico. 5
Division of Genetics, Children's Hospital, Boston, Massachusetts, USA. 6
Department of Ophthalmology, Children's Hospital, Boston, Massachusetts, USA. 7
Genetics Institute, Soroka Medical Center, Ben Gurion University of the Negev, Beer-Sheva, Israel. 8
Department of Medical Biology-Genetics, Arkdeniz University, Turkey. 9
National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA. 10
Scheie Eye Institute, Philadelphia, Pennsylvania, USA. 11
Jules Stein Eye Institute, Harbor-UCLA Medical Center, Torrance, California, USA. 12
Casey Eye Institute, Oregon Health Sciences University, Portland, Oregon, USA.
Correspondence should be addressed to Val C. Sheffield val-sheffield@uiowa.eduBardet-Biedl syndrome (BBS, OMIM 209900) is a genetic disorder with the primary features of obesity, pigmentary retinopathy, polydactyly, renal malformations, mental retardation and hypogenitalism1,
2,
3,
4. Individuals with BBS are also at increased risk for diabetes mellitus, hypertension and congenital heart disease4,
5,
6. What was once thought to be a homogeneous autosomal recessive disorder is now known to map to at least six loci: 11q13 (BBS1), 16q21 (BBS2), 3p13−p12 (BBS3), 15q22.3−q23 (BBS4), 2q31 (BBS5) and 20p12 (BBS6)7,
8,
9,
10,
11,
12,
13. There has been considerable interest in identifying the genes that underlie BBS, because some components of the phenotype are common. Cases of BBS mapping ro BBS6 are caused by mutations in MKKS
12,
13; mutations in this gene also cause McKusick-Kaufman syndrome (hydrometrocolpos, post-axial polydactyly and congenital heart defects)14,
15. In addition, we recently used positional cloning to identify the genes underlying BBS2 (ref. 16) and BBS4 (ref. 17). The BBS6 protein has similarity to a Thermoplasma acidophilum chaperonin15, whereas BBS2 and BBS4 have no significant similarity to chaperonins. It has recently been suggested that three mutated alleles (two at one locus, and a third at a second locus) may be required for manifestation of BBS (triallelic inheritance)18. Here we report the identification of the gene BBS1 and show that a missense mutation of this gene is a frequent cause of BBS. In addition, we provide data showing that this common mutation is not involved in triallelic inheritance.
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