Evaluation of complex inheritance involving the most common Bardet-Biedl syndrome locus (BBS1)

Kirk Mykytyn, Darryl Y. Nishimura, Charles C. Searby, Gretel Beck, Kevin Bugge, Heidi L. Haines, Alberto S. Cornier, Gerald F. Cox, Anne B. Fulton, Rivka Carmi, Alessandro Iannaccone, Samuel G. Jacobson, Richard G. Weleber, Alan F. Wright, Ruth Riise, Raoul C.M. Hennekam, Güven Lüleci, Sibel Berker-Karauzum, Leslie G. Biesecker, Edwin M. StoneVal C. Sheffield

Research output: Contribution to journalArticlepeer-review

97 Scopus citations


Bardet-Biedl syndrome (BBS) is a genetic disorder with the primary features of obesity, pigmentary retinopathy, polydactyly, renal malformations, mental retardation, and hypogenitalism. Patients with BBS are also at increased risk for diabetes mellitus, hypertension, and congenital heart disease. BBS is known to map to at least six loci: 11q13 (BBS1), 16q21 (BBS2), 3p13-p12 (BBS3), 15q22.3-q23 (BBS4), 2q31 (BBSS), and 20p12 (BBS6). Although these loci were all mapped on the basis of an authosomal recessive mode of inheritance, it has recently been suggested - on the basis of mutation analysis of the identified BBS2, BBS4, and BBS6 genes - that BBS displays a complex mode of inheritance in which, in some families, three mutations at two loci are necessary to manifest the disease phenotype. We recently identified BBS1, the gene most commonly involved in Bardet-Biedl syndrome. The identification of this gene allows for further evaluation of complex inheritance. In the present study we evaluate the involvement of the BBS1 gene in a cohort of 129 probands with BBS and report 10 novel BBS1 mutations. We demonstrate that a common BBS1 missense mutation accounts for ∼80% of all BBS1 mutations and is found on a similar genetic background across populations. We show that the BBS1 gene is highly conserved between mice and humans. Finally, we demonstrate that BBS1 is inherited in an authosomal recessive manner and is rarely, if ever, involved in complex inheritance.

Original languageEnglish (US)
Pages (from-to)429-437
Number of pages9
JournalAmerican Journal of Human Genetics
Issue number2
StatePublished - Feb 1 2003

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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