Mutation in PCDH15 may modify the phenotypic expression of the 7511T>C mutation in MT-TS1 in a Chinese Han family with maternally inherited nonsyndromic hearing loss

Int J Pediatr Otorhinolaryngol. 2015 Oct;79(10):1654-7. doi: 10.1016/j.ijporl.2015.07.008. Epub 2015 Jul 11.

Abstract

Objectives: Mutations in MT-TS1 have been found to be associated with nonsyndromic sensorineural hearing loss (SNHL). PCDH15 codes for protocadherin-15, a member of the cadherin superfamily of calcium-dependent cell-cell adhesion molecules. In this study, we analyzed the correlation of both MT-TS1 and PCDH15 mutations in a Chinese Han family segregating maternally inherited nonsyndromic SNHL.

Methods: We ascertained a Chinese Han family segregating maternally inherited nonsyndromic sensorineural hearing loss. Eight of 10 maternal members in this family exhibited late-onset, progressive hearing impairment. Mutation screening of 79 known deafness genes was performed for the proband by targeted next-generation sequencing.

Results: A total of 651 variants were detected in this individual. Among them, a homoplasmic 7511T>C variant in MT-TS1, the mitochondrial tRNA (Ser(UCN)) gene, and a heterozygous p.Asp1010Gly variant in PCDH15 were more likely to be pathogenic. Consistent with the matrilineal inheritance with reduced penetrance, the 7511T>C variant in MT-TS1 was found in all 10 maternal members and an additional heterozygous p.Asp1010Gly variant in PCDH15 cosegregated with the hearing loss in this family.

Conclusion: Our results suggested that the PCDH15 p.Asp1010Gly variant probably modified the phenotypic expression of the 7511T>C mutation in MT-TS1.

Keywords: Hearing loss; Mitochondria; Modifier; Mutation.

MeSH terms

  • Adolescent
  • Adult
  • Asians
  • Cadherin Related Proteins
  • Cadherins / genetics*
  • Female
  • Genes, Mitochondrial / genetics*
  • Hearing Loss, Sensorineural / genetics*
  • Humans
  • Mutation*
  • Pedigree
  • Phenotype
  • RNA, Ribosomal / genetics
  • RNA, Transfer / genetics
  • Young Adult

Substances

  • CDHR15, human
  • Cadherin Related Proteins
  • Cadherins
  • RNA, Ribosomal
  • RNA, Transfer

Supplementary concepts

  • Nonsyndromic sensorineural hearing loss