Biallelic variants in TMIE and PDE6B genes mimic Usher syndrome

Abstract

In the case of consanguineous families, comorbidity cannot be ruled out. Here, we reported a child of eleven years-old who presented profound congenital hearing impairment and progressive visual defect who was suspected to have Usher syndrome. We searched for mutations in Usher syndrome genes but we failed to detect any. We then performed whole exome sequencing to identify the causality of their phenotype. Interestingly, we found two homozygous missense variants, p.(Arg84Trp) in TMIE, responsible for deafness and p.(His337Arg) in PDE6B, responsible for retinitis pigmentosa. The combination of both variants mimics Usher syndrome. This article highlights the importance of genetics in avoiding clinical misdiagnosis, which is important for genetic counseling and in the perspective of gene therapy.