Genotype-phenotype correlation in patients with Usher syndrome and pathogenic variants in MYO7A: implications for future clinical trials

Acta Ophthalmol. 2021 Dec;99(8):922-930. doi: 10.1111/aos.14795. Epub 2021 Feb 11.

Abstract

Purpose: We aimed to establish correlations between the clinical features of a cohort of Usher syndrome (USH) patients with pathogenic variants in MYO7A, type of pathogenic variant, and location on the protein domain.

Methods: Sixty-two USH patients from 46 families with biallelic variants in MYO7A were examined for visual and audiological features. Participants were evaluated based on self-reported ophthalmological history and ophthalmological investigations (computerized visual field testing, best-corrected visual acuity, and ophthalmoscopic and electrophysiological examination). Optical coherence tomography and fundus autofluorescence imaging were performed when possible. Auditory and vestibular functions were evaluated. Patients were classified according to the type of variant and the protein domain where the variants were located.

Results: Most patients displayed a typical USH1 phenotype, that is, prelingual severe-profound sensorineural hearing loss, prepubertal retinitis pigmentosa (RP) and vestibular dysfunction. No statistically significant differences were observed for the variables analysed except for the onset of hearing loss due to the existence of two USH2 cases, defined as postlingual sensorineural hearing loss, postpubertal onset of RP, and absence of vestibular dysfunction, and one atypical case of USH.

Conclusion: We were unable to find a correlation between genotype and phenotype for MYO7A. However, our findings could prove useful for the assessment of efficacy in clinical trials, since the type of MYO7A variant does not seem to change the onset, severity or course of visual disease.

Keywords: MYO7A; Usher syndrome; clinical trials; genetic screening; genotype-phenotype correlation.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Clinical Trials as Topic*
  • DNA / genetics*
  • DNA Mutational Analysis
  • Female
  • Fluorescein Angiography / methods
  • Fundus Oculi
  • Genetic Association Studies / methods*
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Mutation, Missense*
  • Myosin VIIa / genetics*
  • Myosin VIIa / metabolism
  • Pedigree
  • Phenotype
  • Retina / diagnostic imaging
  • Retrospective Studies
  • Tomography, Optical Coherence / methods
  • Usher Syndromes / diagnosis
  • Usher Syndromes / genetics*
  • Young Adult

Substances

  • MYO7A protein, human
  • Myosin VIIa
  • DNA