Mutations in TPRN cause a progressive form of autosomal-recessive nonsyndromic hearing loss

Am J Hum Genet. 2010 Mar 12;86(3):479-84. doi: 10.1016/j.ajhg.2010.02.003. Epub 2010 Feb 18.

Abstract

We performed genome-wide homozygosity mapping in a large consanguineous family from Morocco and mapped the autosomal-recessive nonsyndromic hearing loss (ARNSHL) in this family to the DFNB79 locus on chromosome 9q34. By sequencing of 62 positional candidate genes of the critical region, we identified a causative homozygous 11 bp deletion, c.42_52del, in the TPRN gene in all seven affected individuals. The deletion is located in exon 1 and results in a frameshift and premature protein truncation (p.Gly15AlafsX150). Interestingly, the deleted sequence is part of a repetitive and CG-rich motive predicted to be prone to structural aberrations during crossover formation. We identified another family with progressive ARNSHL linked to this locus, whose affected members were shown to carry a causative 1 bp deletion (c.1347delG) in exon 1 of TPRN. The function of the encoded protein, taperin, is unknown; yet, partial homology to the actin-caping protein phostensin suggests a role in actin dynamics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Chromosome Mapping
  • Chromosomes, Human, Pair 9 / genetics
  • Cochlea / metabolism
  • Consanguinity
  • DNA / genetics
  • DNA Primers / genetics
  • Exons
  • Female
  • Frameshift Mutation
  • Gene Expression
  • Genes, Recessive
  • Hearing Loss / congenital
  • Hearing Loss / genetics*
  • Homozygote
  • Humans
  • Male
  • Mice
  • Morocco
  • Mutation*
  • Pedigree
  • Proteins / genetics*
  • Sequence Deletion

Substances

  • DNA Primers
  • Proteins
  • taperin protein, human
  • DNA