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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 435-438 |
| Number of pages | 4 |
| Journal | Nature Genetics |
| Volume | 31 |
| Issue number | 4 |
| DOIs | |
| State | Published - Aug 1 2002 |
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ASJC Scopus subject areas
- Genetics(clinical)
- Genetics
Cite this
Identification of the gene (BBS1) most commonly involved in Bardet-Biedl syndrome, a complex human obesity syndrome. / Mykytyn, Kirk; Nishimura, Darryl Y.; Searby, Charles C.; Shastri, Mythreyi; Yen, Hsan jan; Beck, John S.; Braun, Terry; Streb, Luan M.; Cornier, Alberto S.; Cox, Gerald F.; Fulton, Anne B.; Carmi, Rivka; Lüleci, Güven; Chandrasekharappa, Settara C.; Collins, Francis S.; Jacobson, Samuel G.; Heckenlively, John R.; Weleber, Richard; Stone, Edwin M.; Sheffield, Val C.
In: Nature Genetics, Vol. 31, No. 4, 01.08.2002, p. 435-438.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Identification of the gene (BBS1) most commonly involved in Bardet-Biedl syndrome, a complex human obesity syndrome
AU - Mykytyn, Kirk
AU - Nishimura, Darryl Y.
AU - Searby, Charles C.
AU - Shastri, Mythreyi
AU - Yen, Hsan jan
AU - Beck, John S.
AU - Braun, Terry
AU - Streb, Luan M.
AU - Cornier, Alberto S.
AU - Cox, Gerald F.
AU - Fulton, Anne B.
AU - Carmi, Rivka
AU - Lüleci, Güven
AU - Chandrasekharappa, Settara C.
AU - Collins, Francis S.
AU - Jacobson, Samuel G.
AU - Heckenlively, John R.
AU - Weleber, Richard
AU - Stone, Edwin M.
AU - Sheffield, Val C.
PY - 2002/8/1
Y1 - 2002/8/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0036699538&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036699538&partnerID=8YFLogxK
U2 - 10.1038/ng935
DO - 10.1038/ng935
M3 - Article
C2 - 12118255
AN - SCOPUS:0036699538
VL - 31
SP - 435
EP - 438
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 4
ER -