Recurrence risks for Bardet-Biedl syndrome: Implications of locus heterogeneity

Julie C Sapp; Darryl Nishimura; Jennifer J Johnston; Edwin M Stone; Elise Héon; Val C Sheffield; Leslie G Biesecker

doi:10.1097/GIM.0b013e3181f07572

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Recurrence risks for Bardet-Biedl syndrome: Implications of locus heterogeneity

Journal article

Open access

Peer reviewed

Recurrence risks for Bardet-Biedl syndrome: Implications of locus heterogeneity

Julie C Sapp, Darryl Nishimura, Jennifer J Johnston, Edwin M Stone, Elise Héon, Val C Sheffield and Leslie G Biesecker

Genetics in medicine, Vol.12(10), pp.623-627

10/2010

DOI: 10.1097/GIM.0b013e3181f07572

PMCID: PMC3115203

PMID: 20949666

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Abstract

Bardet-Biedl syndrome is a pleiotropic multiple anomaly syndrome inherited in an autosomal recessive pattern. It is now known that this disorder has locus heterogeneity, with causative mutations identified in as many as 14 genes. The aim of this study was to derive locus-specific recurrence risk estimates for family members of a proband affected with Bardet-Biedl syndrome. Mutation data from 187 probands affected with Bardet-Biedl syndrome were used. The authors counted the relative proportion of families with mutations at each of 10 loci and estimated locus-specific carrier rates for mutations using Hardy-Weinberg principles and an aggregate population frequency of 1/100,000 for the phenotype. Locus-specific recurrence risks were calculated for relatives of an affected proband. Locus-specific carrier frequencies range from 1/250 to 1/2200, and the risks for an offspring of the sibling of an affected individual range from 1/1,500 to 1/13,000. The estimate of this risk derived under a locus homogeneity model is 1/960. Variation of recurrence risks of this magnitude may have implications for genetic counseling of families with affected individuals, in particular about prenatal testing and other reproductive options. Similar analyses to determine locus-specific carrier frequencies for other phenotypes with significant locus heterogeneity may yield similarly relevant results.

Obesity

Genetic Testing

Risk Assessment

Gene Frequency

Humans

Prenatal Diagnosis

Genetic Loci

Genetic Heterogeneity

Retinitis Pigmentosa

DNA Mutational Analysis

Pedigree

Alleles

Bardet-Biedl Syndrome - diagnosis

Bardet-Biedl Syndrome - genetics

Heterozygote

Models, Genetic

Mutation

Abnormalities, Multiple - genetics

Genetic Carrier Screening

Details

Title: Subtitle: Recurrence risks for Bardet-Biedl syndrome: Implications of locus heterogeneity
Creators: Julie C Sapp - National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA. sappj@mail.nih.gov
Darryl Nishimura
Jennifer J Johnston
Edwin M Stone
Elise Héon
Val C Sheffield
Leslie G Biesecker
Resource Type: Journal article
Publication Details: Genetics in medicine, Vol.12(10), pp.623-627
DOI: 10.1097/GIM.0b013e3181f07572
PMID: 20949666
PMCID: PMC3115203
NLM abbreviation: Genet Med
ISSN: 1098-3600
eISSN: 1530-0366
Publisher: United States
Grant note: R01 EY011298 / NEI NIH HHS ZIA HG200328-06 / Intramural NIH HHS Howard Hughes Medical Institute R01 EY017168 / NEI NIH HHS R01-EY-11298 / NEI NIH HHS
Language: English
Date published: 10/2010
Academic Unit: Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
Record Identifier: 9983980078102771

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