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

  • Shujiro B. Minami
    Affiliations
    National Hospital Organization Tokyo Medical Center, Department of Otolaryngology, 2-5-1 Higashigaoka, Meguroku, Tokyo 152-8901, Japan

    National Hospital Organization Tokyo Medical Center, National Institute of Sensory Organs, 2-5-1 Higashigaoka, Meguroku, Tokyo 152-8901, Japan
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  • Hideki Mutai
    Affiliations
    National Hospital Organization Tokyo Medical Center, National Institute of Sensory Organs, 2-5-1 Higashigaoka, Meguroku, Tokyo 152-8901, Japan
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  • Kazunori Namba
    Affiliations
    National Hospital Organization Tokyo Medical Center, National Institute of Sensory Organs, 2-5-1 Higashigaoka, Meguroku, Tokyo 152-8901, Japan
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  • Hirokazu Sakamoto
    Affiliations
    Hyogo Prefectural Kobe Children's Hospital, Department of Otolaryngology, 1-1-1 Takakuradai, Sumaku, Koube, Hyogo 654-0091, Japan
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  • Tatsuo Matsunaga
    Correspondence
    Corresponding author at: National Hospital Organization Tokyo Medical Center, National Institute of Sensory Organs, Laboratory of Auditory Disorders, 2-5-1 Higashigaoka, Meguroku, Tokyo 152-8901, Japan. Tel.: +81 3 3411 0111; fax: +81 3 3412 9811.
    Affiliations
    National Hospital Organization Tokyo Medical Center, Department of Otolaryngology, 2-5-1 Higashigaoka, Meguroku, Tokyo 152-8901, Japan

    National Hospital Organization Tokyo Medical Center, National Institute of Sensory Organs, 2-5-1 Higashigaoka, Meguroku, Tokyo 152-8901, Japan
    Search for articles by this author
Published:March 10, 2016DOI:https://doi.org/10.1016/j.anl.2016.02.010

      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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