Identification of the gene (BBS1) most commonly involved in Bardet-Biedl syndrome, a complex human obesity syndrome.
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.
Mykytyn
Kirk
K
Department of Pediatrics, Division of Medical Genetics and the Howard Hughes Medical Institute, University of Iowa, Iowa City, Iowa 52242, USA.
Nishimura
Darryl Y
DY
Searby
Charles C
CC
Shastri
Mythreyi
M
Yen
Hsan-jan
HJ
Beck
John S
JS
Braun
Terry
T
Streb
Luan M
LM
Cornier
Alberto S
AS
Cox
Gerald F
GF
Fulton
Anne B
AB
Carmi
Rivka
R
Lüleci
Güven
G
Chandrasekharappa
Settara C
SC
Collins
Francis S
FS
Jacobson
Samuel G
SG
Heckenlively
John R
JR
Weleber
Richard G
RG
Stone
Edwin M
EM
Sheffield
Val C
VC
D020788:Bardet-Biedl Syndrome / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D006720:Homozygote; D006801:Humans; D008869:Microtubule-Associated Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics* / Q000378:metabolism
C464790:Bbs1 protein, human; D008869:Microtubule-Associated Proteins; D011506:Proteins