Mutations in LOXHD1 gene cause various types and severities of hearing loss

Ann Otol Rhinol Laryngol. 2015 May;124 Suppl 1(1 0):135S-41S. doi: 10.1177/0003489415574067. Epub 2015 Mar 19.

Abstract

Objective: We present 2 families that were identified with novel mutations in LOXHD1 as a cause of nonprogressive hearing loss.

Methods: One thousand three hundred fourteen (1314) Japanese subjects with sensorineural hearing loss from unrelated families were enrolled in the study. Targeted genomic enrichment and massively parallel sequencing of all known nonsyndromic hearing loss genes were performed to identify the genetic cause of hearing loss.

Results: Two patients in 1 family affected with homozygous mutation c.879+1G>A in LOXHD1 showed profound congenital hearing loss, whereas 2 patients in another family with compound heterozygous mutations, c.5869G>T (p.E1957X) and c.4480C>T (p.R1494X), showed moderate to severe hearing loss.

Conclusion: Mutations in LOXHD1 are extremely rare, and these cases are the first identified in a Japanese population. The genotype-phenotype correlation in LOXHD1 is still unclear. The differences in phenotypes in each patient might be the result of the nature of the mutations or the location on the gene, or be influenced by a genetic modifier.

Keywords: DFNB77; LOXHD1; genetics; hearing loss; massively parallel sequencing.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People / genetics
  • Audiometry, Pure-Tone
  • Carrier Proteins / genetics*
  • Child
  • Deafness / genetics
  • Genes, Recessive
  • Genetic Association Studies
  • Hearing Loss, Sensorineural / genetics*
  • High-Throughput Nucleotide Sequencing*
  • Humans
  • Male
  • Pedigree
  • Sequence Analysis, DNA / methods

Substances

  • Carrier Proteins
  • LOXHD1 protein, human

Supplementary concepts

  • Nonsyndromic Deafness