Identification of a novel MYO7A gene mutation in a family with late-onset autosomal dominant nonsyndromic sensorineural hearing loss

ZUO Yangjin; WEN Chunxiu; HE Sheng; QIN Zailong; YANG Qi; YI Shang; CHEN Biyan

doi:10.3969/j.issn.1674-3806.2025.02.14

Abstract：Objective To identify a novel MYO7A gene mutation in a family with late-onset autosomal dominant nonsyndromic sensorineural hearing loss.Methods The clinical data of a proband and her family members were collected and the family genogram were drawn.Hearing examination was performed on the proband and her family members.Genome whole-exome sequencing was performed on the proband to locate the targeted deafness gene and mutation,and MYO7A gene of the proband and her family members was verified by Sanger sequencing.Results The proband developed the disease at the age of 16 and was diagnosed with bilateral severe sensorineural hearing loss.There were 18 patients with post-lingual progressive hearing loss in the proband's family members,characterized by autosomal dominant inheritance.The patients'age at onset varied among different individuals and differed between families and between generations.The onset age of patients with deafness in generation Ⅳ and generation Ⅴ was significantly younger than that of patients with deafness in generation Ⅲ(P＜0.05),showing a tendency of genetic early onset.The average pure-tone audiometric threshold in both ears of the proband was 83 dBHL(air conduction),and the maximum intensity of bone conduction in each frequency band showed no response,with more pronounced losses in the mid-to-high frequency ranges.A heterozygous mutation of c.689C＞T in exon 7 of MYO7A gene was located by using whole-exome sequencing.Sanger sequencing confirmed that the mutation was detected in the proband and the deaf family members of the proband.Conclusion This paper reports a case of hereditary non-syndromic hearing loss caused by the heterozygous mutation of c.689C＞T in exon 7 of MYO7A gene in a pedigree and discovers a unique genetic early onset phenomenon of this mutation in the family genogram in China.