title: Clinical and genetic characterization of Bardet-Biedl syndrome in Tunisia: defining a strategy for molecular diagnosis.
abstract: Bardet-Biedl syndrome (BBS, OMIM 209900) is a rare genetic disorder characterized by obesity, retinitis pigmentosa, post axial polydactyly, cognitive impairment, renal anomalies and hypogonadism. The aim of this study is to provide a comprehensive clinical and molecular analysis of a cohort of 11 Tunisian BBS consanguineous families in order to give insight into clinical and genetic spectrum and the genotype-phenotype correlations. Molecular analysis using combined sequence capture and high-throughput sequencing of 30 ciliopathies genes revealed 11 mutations in 11 studied families. Five mutations were novel and six were previously described. Novel mutations included c.1110G>A and c.39delA (p.G13fs*41) in BBS1, c.115+5G>A in BBS2, c.1272+1G>A in BBS6, c.1181_1182insGCATTTATACC in BBS10 (p.S396Lfs*6). Described mutations included c.436C>T (p.R146*) and c.1473+4A>G in BBS1, c.565C> (p.R189*) in BBS2, deletion of exons 4-6 in BBS4, c.149T>G (p.L50R) in BBS5, and c.459+1G>A in BBS8; most frequent mutations were described in BBS1 (4/11, 37%) and BBS2 (2/11, 18%) genes. No phenotype-genotype correlation was evidenced. This data expands the mutations profile of BBS genes in Tunisia and suggests a divergence of the genetic spectrum comparing Tunisian and other populations.
authors: Faculté de médecine de Tunis, Université de Tunis El-Manar, Tunis, Tunisie.
authors: O
authors: O
authors: M'hamdi
authors: C
authors: C
authors: Redin
authors: C
authors: C
authors: Stoetzel
authors: I
authors: I
authors: Ouertani
authors: M
authors: M
authors: Chaabouni
authors: F
authors: F
authors: Maazoul
authors: R
authors: R
authors: M'rad
authors: J L
authors: JL
authors: Mandel
authors: H
authors: H
authors: Dollfus
authors: J
authors: J
authors: Muller
authors: H
authors: H
authors: Chaabouni
mesh_terms: D020788:Bardet-Biedl Syndrome / Q000235:genetics* / Q000473:pathology*; D001483:Base Sequence; D018833:Chaperonins; D019295:Computational Biology; D056385:Group II Chaperonins / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D014416:Tunisia
chemical_list: C512111:BBS10 protein, human; C464790:Bbs1 protein, human; C473309:Bbs2 protein, human; C414726:MKKS protein, human; D008869:Microtubule-Associated Proteins; D011506:Proteins; D018833:Chaperonins; D056385:Group II Chaperonins
keywords: Bardet-Biedl syndrome; genotype-phenotype correlation; mutation; next generation sequencing