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 Weleber, Edwin M. Stone, Val C. Sheffield

Research output: Contribution to journalArticle

237 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)435-438
Number of pages4
JournalNature Genetics
Volume31
Issue number4
DOIs
StatePublished - Aug 1 2002

Fingerprint

Bardet-Biedl Syndrome
Obesity
Chaperonins
Polydactyly
Genes
Mutation
Thermoplasma
Genetic Databases
Inborn Genetic Diseases
Retinitis Pigmentosa
Congenital Heart Defects
Missense Mutation
Intellectual Disability
Organism Cloning
Heart Diseases
Diabetes Mellitus
Alleles
Hypertension
Phenotype
Kidney

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Mykytyn, K., Nishimura, D. Y., Searby, C. C., Shastri, M., Yen, H. J., Beck, J. S., ... Sheffield, V. C. (2002). Identification of the gene (BBS1) most commonly involved in Bardet-Biedl syndrome, a complex human obesity syndrome. Nature Genetics, 31(4), 435-438. https://doi.org/10.1038/ng935

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 journalArticle

Mykytyn, K, Nishimura, DY, Searby, CC, Shastri, M, Yen, HJ, Beck, JS, Braun, T, Streb, LM, Cornier, AS, Cox, GF, Fulton, AB, Carmi, R, Lüleci, G, Chandrasekharappa, SC, Collins, FS, Jacobson, SG, Heckenlively, JR, Weleber, R, Stone, EM & Sheffield, VC 2002, 'Identification of the gene (BBS1) most commonly involved in Bardet-Biedl syndrome, a complex human obesity syndrome', Nature Genetics, vol. 31, no. 4, pp. 435-438. https://doi.org/10.1038/ng935
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. / Identification of the gene (BBS1) most commonly involved in Bardet-Biedl syndrome, a complex human obesity syndrome. In: Nature Genetics. 2002 ; Vol. 31, No. 4. pp. 435-438.
@article{b57b6435c2b84b52b3ec3ff34683f5c6,
title = "Identification of the gene (BBS1) most commonly involved in Bardet-Biedl syndrome, a complex human obesity syndrome",
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.",
author = "Kirk Mykytyn and Nishimura, {Darryl Y.} and Searby, {Charles C.} and Mythreyi Shastri and Yen, {Hsan jan} and Beck, {John S.} and Terry Braun and Streb, {Luan M.} and Cornier, {Alberto S.} and Cox, {Gerald F.} and Fulton, {Anne B.} and Rivka Carmi and G{\"u}ven L{\"u}leci and Chandrasekharappa, {Settara C.} and Collins, {Francis S.} and Jacobson, {Samuel G.} and Heckenlively, {John R.} and Richard Weleber and Stone, {Edwin M.} and Sheffield, {Val C.}",
year = "2002",
month = "8",
day = "1",
doi = "10.1038/ng935",
language = "English (US)",
volume = "31",
pages = "435--438",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "4",

}

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 -