title: A founder mutation in BBS2 is responsible for Bardet-Biedl syndrome in the Hutterite population: utility of SNP arrays in genetically heterogeneous disorders.
abstract: 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.
authors.affiliation: Department of Medical Genetics, Alberta Children's Hospital and University of Calgary, Calgary, Alberta, Canada.
authors.forename: A M
authors.initials: AM
authors.lastname: Innes
authors.forename: K M
authors.initials: KM
authors.lastname: Boycott
authors.forename: E G
authors.initials: EG
authors.lastname: Puffenberger
authors.forename: D
authors.initials: D
authors.lastname: Redl
authors.forename: I M
authors.initials: IM
authors.lastname: MacDonald
authors.forename: A E
authors.initials: AE
authors.lastname: Chudley
authors.forename: C
authors.initials: C
authors.lastname: Beaulieu
authors.forename: R
authors.initials: R
authors.lastname: Perrier
authors.forename: T
authors.initials: T
authors.lastname: Gillan
authors.forename: A
authors.initials: A
authors.lastname: Wade
authors.forename: J S
authors.initials: JS
authors.lastname: Parboosingh
mesh_terms: D000293:Adolescent; D000328:Adult; D020788:Bardet-Biedl Syndrome / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005006:Ethnicity / Q000235:genetics*; D018703:Founder Effect; D055106:Genome-Wide Association Study; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D020641:Polymorphism, Single Nucleotide; D022821:RNA Splice Sites / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: D022821:RNA Splice Sites