Identification of novel <i>MYH14</i> variants in families with autosomal dominant sensorineural hearing loss

DUMAN D., Ramzan M., Subasioglu A., MUTLU A., Peart L., Seyhan S., ...Daha Fazla

AMERICAN JOURNAL OF MEDICAL GENETICS PART A, cilt.194, sa.6, 2024 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 194 Sayı: 6
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1002/ajmg.a.63563
  • Dergi Adı: AMERICAN JOURNAL OF MEDICAL GENETICS PART A
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Applied Science & Technology Source, BIOSIS, CAB Abstracts, EMBASE, MEDLINE
  • Anahtar Kelimeler: gene, hearing loss, MYH14, pathogenic variant
  • Ankara Üniversitesi Adresli: Hayır

Özet

Autosomal dominant sensorineural hearing loss (ADSNHL) is a genetically heterogeneous disorder caused by pathogenic variants in various genes, including MYH14. However, the interpretation of pathogenicity for MYH14 variants remains a challenge due to incomplete penetrance and the lack of functional studies and large families. In this study, we performed exome sequencing in six unrelated families with ADSNHL and identified five MYH14 variants, including three novel variants. Two of the novel variants, c.571G > C (p.Asp191His) and c.571G > A (p.Asp191Asn), were classified as likely pathogenic using ACMG and Hearing Loss Expert panel guidelines. In silico modeling demonstrated that these variants, along with p.Gly1794Arg, can alter protein stability and interactions among neighboring molecules. Our findings suggest that MYH14 causative variants may be more contributory and emphasize the importance of considering this gene in patients with nonsyndromic mainly post-lingual severe form of hearing loss. However, further functional studies are needed to confirm the pathogenicity of these variants.