Clinical and genetic characterization of Bardet-Biedl syndrome in Tunisia: defining a strategy for molecular diagnosis

Clin Genet. 2014 Feb;85(2):172-7. doi: 10.1111/cge.12129. Epub 2013 Apr 5.

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.

Keywords: Bardet-Biedl syndrome; genotype-phenotype correlation; mutation; next generation sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bardet-Biedl Syndrome / genetics*
  • Bardet-Biedl Syndrome / pathology*
  • Base Sequence
  • Chaperonins
  • Computational Biology
  • Group II Chaperonins / genetics*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Microtubule-Associated Proteins / genetics*
  • Molecular Sequence Data
  • Phenotype*
  • Proteins / genetics*
  • Tunisia

Substances

  • BBS10 protein, human
  • Bbs1 protein, human
  • Bbs2 protein, human
  • MKKS protein, human
  • Microtubule-Associated Proteins
  • Proteins
  • Chaperonins
  • Group II Chaperonins