Novel and recurrent MYO7A mutations in Usher syndrome type 1 and type 2

Area of Science:

• Genetics
• Ophthalmology
• Audiology

Background:

• Usher syndrome (USH) is a genetic disorder causing retinitis pigmentosa and hearing loss.
• Autosomal recessive USH presents with variable vestibular dysfunction.
• Genetic mutations are the primary cause of inherited retinal diseases.

Purpose of the Study:

• To identify causative mutations in three Chinese families with autosomal recessive USH.
• To investigate the genotype-phenotype relationship in USH, particularly involving the MYO7A gene.
• To evaluate the efficacy of targeted next-generation sequencing (NGS) for USH diagnosis.

Main Methods:

• Recruitment of three Chinese families affected with autosomal recessive USH.
• Comprehensive clinical evaluations and targeted next-generation sequencing (NGS) for mutation screening.
• Crystal structural analysis to predict the impact of identified mutations.

Main Results:

• Three novel alleles and one known mutation in the MYO7A gene were identified across the three families.
• Novel mutations (p.Pro194Hisfs*13, p.Thr165Met, c.[1343+1G>A];[2837T>G]) were found in MYO7A, causative for USH types 1 and 2.
• The p.Thr165Met mutation is predicted to alter the MYO7A protein structure; MYO7A mutations were identified in a USH type 2 family, expanding known genotype-phenotype correlations.

Conclusions:

• Targeted NGS is an effective method for the genetic diagnosis of Usher syndrome.
• The study identified novel MYO7A mutations and expanded the understanding of its role in USH types 1 and 2.
• Findings highlight distinct clinical phenotypes associated with MYO7A mutations, enhancing genotype-phenotype correlation knowledge.