Clinical Heterogeneity Associated with MYO7A Variants Relies on Affected Domains

Sun Young Joo, Gina Na, Jung Ah Kim, Jee Eun Yoo, Da Hye Kim, Se Jin Kim, Seung Hyun Jang, Seyoung Yu, Hye Youn Kim, Jae Young Choi, Heon Yung Gee, Jinsei Jung

Research output: Contribution to journalArticlepeer-review

Abstract

Autosomal dominant hearing loss (ADHL) manifests as an adult-onset disease or a progressive disease. MYO7A variants are associated with DFNA11, a subtype of ADHL. Here, we examined the role and genotype–phenotype correlation of MYO7A in ADHL. Enrolled families suspected of having post-lingual sensorineural hearing loss were selected for exome sequencing. Mutational alleles in MYO7A were identified according to ACMG guidelines. Segregation analysis was performed to examine whether pathogenic variants segregated with affected status of families. All identified pathogenic variants were evaluated for a phenotype–genotype correlation. MYO7A variants were detected in 4.7% of post-lingual families, and 12 of 14 families were multiplex. Five potentially pathogenic missense variants were identified. Fourteen variants causing autosomal dominant deafness were clustered in motor and MyTH4 domains of MYO7A protein. Missense variants in the motor domain caused late onset of hearing loss with ascending tendency. A severe audiological phenotype was apparent in individuals carrying tail domain variants. We report two new pathogenic variants responsible for DFNA11 in the Korean ADHL population. Dominant pathogenic variants of MYO7A occur frequently in motor and MyTH4 domains. Audiological differences among individuals correspond to specific domains which contain the variants. Therefore, appropriate rehabilitation is needed, particularly for patients with late-onset familial hearing loss.

Original languageEnglish
Article number798
JournalBiomedicines
Volume10
Issue number4
DOIs
Publication statusPublished - 2022 Apr

Bibliographical note

Funding Information:
This study was supported by the Yonsei University College of Medicine (Team Science Award 6-2021-0003 to H.Y.G. and 6-2021-0002 to J.J.) and by the National Research Foundation of Korea (NRF) (2018R1A5A2025079 to H.Y.G and 2019R1A2C1084033 to J.J.).

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint

Dive into the research topics of 'Clinical Heterogeneity Associated with MYO7A Variants Relies on Affected Domains'. Together they form a unique fingerprint.

Cite this