A founder mutation in BBS2 is responsible for Bardet‐Biedl syndrome in the Hutterite population: utility of SNP arrays in genetically heterogeneous disorders |
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| Authors: | AM Innes KM Boycott EG Puffenberger D Redl IM MacDonald AE Chudley C Beaulieu R Perrier T Gillan A Wade JS Parboosingh |
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| Affiliation: | 1. Department of Medical Genetics, Alberta Children's Hospital and University of Calgary, Calgary, Alberta, Canada;2. Department of Pediatrics, University of Ottawa and Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada;3. Clinic for Special Children, Strasburg, PA, USA;4. Franklin and Marshall College, Lancaster, PA, USA;5. Department of Ophthalmology, University of Alberta, Edmonton, Alberta, Canada;6. Section of Genetics and Metabolism, Children's Hospital and Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada;7. Department of Pathology and Laboratory Medicine, Vancouver General Hospital, University of British Columbia, Vancouver, British Columbia, Canada,;8. Department of Pediatrics, Alberta Children's Hospital and University of Calgary, Calgary, Alberta, Canada |
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| Abstract: | ![]()
Innes AM, Boycott KM, Puffenberger EG, Redl D, MacDonald IM, Chudley AE, Beaulieu C, Perrier R, Gillan T, Wade A, Parboosingh JS. A founder mutation in BBS2 is responsible for Bardet‐Biedl syndrome in the Hutterite population: utility of SNP arrays in genetically heterogeneous disorders. Bardet‐Biedl syndrome (BBS) is a multisystem genetically heterogeneous disorder, the clinical features of which are largely the consequence of ciliary dysfunction. BBS is typically inherited in an autosomal recessive fashion, and mutations in at least 14 genes have been identified. Here, we report the identification of a founder mutation in the BBS2 gene as the cause for the increased incidence of this developmental disorder in the Hutterite population. To ascertain the Hutterite BBS locus, we performed a genome‐wide single nucleotide polymorphism (SNP) analysis on a single patient and his three unaffected siblings from a Hutterite family. The analysis identified two large SNP blocks that were homozygous in the patient but not in his unaffected siblings, one of these regions contained the BBS2 gene. Sequence analysis and subsequent RNA studies identified and confirmed a novel splice site mutation, c.472‐2A>G, in BBS2. This mutation was also found in homozygous form in three subsequently studied Hutterite BBS patients from two different leuts, confirming that this is a founder mutation in the Hutterite population. Further studies are required to determine the frequency of this mutation and its role, if any, in the expression of other ciliopathies in this population. |
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| Keywords: | Bardet‐Biedl syndrome Hutterite identity‐by‐descent mapping SNP microarray |
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