Abstract
The genetic, mutational and phenotypic spectrum of deafness-causing genes shows great diversity and pleiotropy. The best examples are the group of genes, which when mutated can either cause non-syndromic hearing loss (NSHL) or the most common dual sensory impairment, Usher Syndrome (USH). Variants in the
CIB2
gene have been previously reported to cause of hearing loss at the DFNB48 locus and deaf-blindness at the USH1J locus. In this study, we characterize the phenotypic spectrum in a multiethnic cohort with autosomal recessive non-syndromic hearing loss (ARNSHL) due to variants in the
CIB2
gene. Of the 6 families we ascertained, 3 segregated novel loss-of-function variants, 2 families segregated missense variants (one novel) and 1 family segregated a previously reported pathogenic variant in
trans
with a frameshift variant. This report is the first to show that biallelic loss of function variants in
CIB2
cause ARNSHL and not USH. In the era of precision medicine, providing the correct diagnosis (NSHL vs USH) is essential for patient care as it impacts potential intervention and prevention options for patients. Here we provide evidence disqualifying
CIB2
as an USH-causing gene.
