Sequence variants in four genes underlying Bardet-Biedl syndrome in consanguineous families

Mol Vis. 2017 Jul 21:23:482-494. eCollection 2017.

Abstract

Purpose: To investigate the molecular basis of Bardet-Biedl syndrome (BBS) in five consanguineous families of Pakistani origin.

Methods: Linkage in two families (A and B) was established to BBS7 on chromosome 4q27, in family C to BBS8 on chromosome 14q32.1, and in family D to BBS10 on chromosome 12q21.2. Family E was investigated directly with exome sequence analysis.

Results: Sanger sequencing revealed two novel mutations and three previously reported mutations in the BBS genes. These mutations include two deletions (c.580_582delGCA, c.1592_1597delTTCCAG) in the BBS7 gene, a missense mutation (p.Gln449His) in the BBS8 gene, a frameshift mutation (c.271_272insT) in the BBS10 gene, and a nonsense mutation (p.Ser40*) in the MKKS (BBS6) gene.

Conclusions: Two novel mutations and three previously reported variants, identified in the present study, further extend the body of evidence implicating BBS6, BBS7, BBS8, and BBS10 in causing BBS.

MeSH terms

  • Abnormalities, Multiple / diagnosis
  • Abnormalities, Multiple / genetics
  • Adaptor Proteins, Signal Transducing
  • Adolescent
  • Adult
  • Bardet-Biedl Syndrome / diagnosis
  • Bardet-Biedl Syndrome / genetics*
  • Chaperonins
  • Child
  • Codon, Nonsense
  • Consanguinity*
  • Cytoskeletal Proteins
  • DNA Mutational Analysis
  • Female
  • Frameshift Mutation
  • Genetic Linkage
  • Genetic Testing
  • Group II Chaperonins / genetics*
  • Humans
  • Male
  • Mutation*
  • Mutation, Missense
  • Pedigree
  • Proteins / genetics*
  • Sequence Analysis, DNA
  • Sequence Deletion
  • Young Adult

Substances

  • Adaptor Proteins, Signal Transducing
  • BBS10 protein, human
  • Bbs7 protein, human
  • Codon, Nonsense
  • Cytoskeletal Proteins
  • MKKS protein, human
  • Proteins
  • TTC8 protein, human
  • Chaperonins
  • Group II Chaperonins