Identification of the gene (BBS1) most commonly involved in Bardet-Biedl syndrome, a complex human obesity syndrome

Kirk Mykytyn; Darryl Y Nishimura; Charles C Searby; Mythreyi Shastri; Hsan-jan Yen; John S Beck; Terry Braun; Luan M Streb; Alberto S Cornier; Gerald F Cox; Anne B Fulton; Rivka Carmi; Güven Lüleci; Settara C Chandrasekharappa; Francis S Collins; Samuel G Jacobson; John R Heckenlively; Richard G Weleber; Edwin M Stone; Val C Sheffield

doi:10.1038/ng935

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Identification of the gene (BBS1) most commonly involved in Bardet-Biedl syndrome, a complex human obesity syndrome

Journal article

Peer reviewed

Identification of the gene (BBS1) most commonly involved in Bardet-Biedl syndrome, a complex human obesity syndrome

Kirk Mykytyn, Darryl Y Nishimura, Charles C Searby, Mythreyi Shastri, Hsan-jan Yen, John S Beck, Terry Braun, Luan M Streb, Alberto S Cornier, Gerald F Cox, …

Nature genetics, Vol.31(4), pp.435-438

08/2002

DOI: 10.1038/ng935

PMID: 12118255

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Abstract

Bardet-Biedl syndrome (BBS, OMIM 209900) is a genetic disorder with the primary features of obesity, pigmentary retinopathy, polydactyly, renal malformations, mental retardation and hypogenitalism. Individuals with BBS are also at increased risk for diabetes mellitus, hypertension and congenital heart disease. 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). 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; mutations in this gene also cause McKusick-Kaufman syndrome (hydrometrocolpos, post-axial polydactyly and congenital heart defects). 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 chaperonin, 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). 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.

Mutation

Polymorphism, Single-Stranded Conformational

Proteins - genetics

Homozygote

Proteins - metabolism

Gene Expression Regulation, Developmental

Pedigree

Humans

Microtubule-Associated Proteins

Molecular Sequence Data

Bardet-Biedl Syndrome - genetics

Mutation, Missense

Details

Title: Subtitle: Identification of the gene (BBS1) most commonly involved in Bardet-Biedl syndrome, a complex human obesity syndrome
Creators: Kirk Mykytyn - Department of Pediatrics, Division of Medical Genetics and the Howard Hughes Medical Institute, University of Iowa, Iowa City, Iowa 52242, USA
Darryl Y Nishimura
Charles C Searby
Mythreyi Shastri
Hsan-jan Yen
John S Beck
Terry Braun
Luan M Streb
Alberto S Cornier
Gerald F Cox - Boston Children's Hospital
Anne B Fulton
Rivka Carmi
Güven Lüleci
Settara C Chandrasekharappa
Francis S Collins
Samuel G Jacobson
John R Heckenlively
Richard G Weleber
Edwin M Stone
Val C Sheffield
Resource Type: Journal article
Publication Details: Nature genetics, Vol.31(4), pp.435-438
DOI: 10.1038/ng935
PMID: 12118255
NLM abbreviation: Nat Genet
ISSN: 1061-4036
eISSN: 1546-1718
Publisher: United States
Language: English
Date published: 08/2002
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Electrical and Computer Engineering; Stead Family Department of Pediatrics; The University of Iowa Institute for Vision Research; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
Record Identifier: 9983979961402771

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