Evaluation of complex inheritance involving the most common Bardet-Biedl syndrome locus (BBS1).
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 (BBS5), and 20p12 (BBS6). Although these loci were all mapped on the basis of an autosomal 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 approximately 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 autosomal recessive manner and is rarely, if ever, involved in complex inheritance.
Mykytyn
Kirk
K
Department of Pediatrics, Division of Medical Genetics, and Howard Hughes Medical Institute, University of Iowa, Iowa City, IA, 52242, USA.
Nishimura
Darryl Y
DY
Searby
Charles C
CC
Beck
Gretel
G
Bugge
Kevin
K
Haines
Heidi L
HL
Cornier
Alberto S
AS
Cox
Gerald F
GF
Fulton
Anne B
AB
Carmi
Rivka
R
Iannaccone
Alessandro
A
Jacobson
Samuel G
SG
Weleber
Richard G
RG
Wright
Alan F
AF
Riise
Ruth
R
Hennekam
Raoul C M
RC
Lüleci
Güven
G
Berker-Karauzum
Sibel
S
Biesecker
Leslie G
LG
Stone
Edwin M
EM
Sheffield
Val C
VC
D000595:Amino Acid Sequence; D000818:Animals; D020788:Bardet-Biedl Syndrome / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11; D015331:Cohort Studies; D017124:Conserved Sequence; D019143:Evolution, Molecular; D005808:Genes, Recessive; D006239:Haplotypes; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010802:Phylogeny; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
C464790:Bbs1 protein, human; D008869:Microtubule-Associated Proteins; D011506:Proteins