Abstract
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
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Article info
Publication history
Published online: March 10, 2016
Accepted:
February 15,
2016
Received:
September 17,
2015
Identification
Copyright
© 2016 Elsevier Ireland Ltd. All rights reserved.
