Novel mutation located in EC7 domain of protocadherin-15 uncovered by targeted massively parallel sequencing in a family segregating non-syndromic deafness DFNB23

Int J Pediatr Otorhinolaryngol. 2015 Jul;79(7):983-6. doi: 10.1016/j.ijporl.2015.04.002. Epub 2015 Apr 11.

Abstract

Objective: Hereditary hearing loss is a clinically and genetically heterogeneous disorder associated with mutations of a large number of diverse genes. In this study we applied targeted capture and massively parallel sequencing to identify the disease-causing gene of a Chinese family segregating recessive inherited deafness.

Methods: After excluding mutations in common deafness genes GJB2, SLC26A4, mitochondrial m.1555A>G, genomic DNA of the proband of family GDSW24 was subjected to targeted next-generation sequencing. Subsequently, a candidate homozygous mutation was confirmed by Sanger sequencing.

Results: A novel PCDH15 c.2367_2369delTGT/p.V788-homozygous mutation was detected. In this family, no obvious vestibular disorder was found. The in-frame mutation c.2367_2369delTGT is located in the evolutionarily conserved EC7 domain of Protocadherin-15 and was predicted to be pathogenic.

Conclusion: The novel homozygous mutation in a family segregating non-syndromic hearing loss family supports previous reported observations that PCDH15 does not only causes Usher syndrome type 1F, but also DFNB23.

Keywords: DFNB23; PCDH15; Protocadherin-15; Targeted next-generation sequencing.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cadherin Related Proteins
  • Cadherins / genetics*
  • Connexin 26
  • Connexins
  • Female
  • Genetic Markers
  • Genetic Testing / methods
  • Hearing Loss, Sensorineural / genetics*
  • High-Throughput Nucleotide Sequencing
  • Homozygote
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Young Adult

Substances

  • CDHR15, human
  • Cadherin Related Proteins
  • Cadherins
  • Connexins
  • GJB2 protein, human
  • Genetic Markers
  • Connexin 26

Supplementary concepts

  • Deafness, Autosomal Recessive 23