Clinical characteristics of a Japanese family with hearing loss accompanied by compound heterozygous mutations in LOXHD1

Auris Nasus Larynx. 2016 Dec;43(6):609-13. doi: 10.1016/j.anl.2016.02.010. Epub 2016 Mar 10.


Objective: To report two novel LOXHD1 mutations, including missense mutations and the clinical features of the patients.

Methods: We studied a three-generation Japanese family with hearing loss. Targeted next-generation sequencing was used for genetic analysis. Conditional orientation response audiometry and pure tone audiometry were used to assess hearing. SWISS-MODEL was used for molecular modeling of the PLAT domain in LOXHD1 protein.

Results: The two sisters, who had either mild or severe high-frequency hearing loss, were compound heterozygous for two novel mutations (c.5674G>T [p.V1892F] and c.4212+1G>A) in LOXHD1, which is responsible for autosomal-recessive nonsyndromic hearing loss DFNB77. These cases showed less severe hearing impairment than the previously reported cases carrying LOXHD1 mutations, but their hearing loss appeared to be progressive. Molecular modeling predicted that distorted structure of the PLAT domain in the p.V1892F mutant could lead to decreased affinity of the protein to lipid membrane resulting in hair cell dysfunction.

Conclusion: We report a Japanese family carrying compound heterozygotes of truncating and nontruncating mutations in LOXHD1 identified by targeted NGS analysis. The fact of lower degree of hearing impairment in our cases than previously reported and the molecular modeling of the missense mutant provide insight to the genotype-phenotype correlation of DFNB77.

Keywords: Autosomal-recessive nonsyndromic hearing loss; DFNB77; LOXHD1; Molecular modeling; PLAT domain; Targeted next-generation sequencing.

Publication types

  • Case Reports

MeSH terms

  • Asian People / genetics
  • Audiometry
  • Audiometry, Pure-Tone
  • Carrier Proteins / genetics*
  • Child
  • DNA Mutational Analysis
  • Female
  • Genotype
  • Hearing Loss, High-Frequency / genetics*
  • Hearing Loss, Sensorineural / genetics*
  • Heterozygote
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Infant
  • Japan
  • Mutation, Missense*
  • Pedigree
  • Phenotype
  • Siblings*


  • Carrier Proteins
  • LOXHD1 protein, human

Supplementary concepts

  • Deafness, Autosomal Recessive 77