Identification of Novel Compound Heterozygous MYO15A Mutations in Two Chinese Families with Autosomal Recessive Nonsyndromic Hearing Loss

Abstract

Congenital deafness is one of the most common causes of disability in humans, and more than half of cases are caused by genetic factors. Mutations of the MYO15A gene are the third most common cause of hereditary hearing loss. Using next-generation sequencing combined with auditory tests, two novel compound heterozygous variants c.2802_2812del/c.5681T>C and c.5681T>C/c.6340G>A in the MYO15A gene were identified in probands from two irrelevant Chinese families. Auditory phenotypes of the probands are consistent with the previously reported for recessive variants in the MYO15A gene. The two novel variants, c.2802_2812del and c.5681T>C, were identified as deleterious mutations by bioinformatics analysis. Our findings extend the MYO15A gene mutation spectrum and provide more information for rapid and precise molecular diagnosis of congenital deafness.

Exome-wide evidence of compound heterozygous effects across common phenotypes in the UK Biobank

“…CH disease associations have mainly been explored in rare disorders, 13 , 14 , 15 , 16 , 17 but they seldom have been investigated in the study of common disease. This is due to the low prevalence of variants in the CH state and the genetic architecture of common complex traits, which are typically influenced by environmental factors and numerous loci with low to modest contribution to risk.…”

“… 12 In contrast, CH is expected to be more common in outbred populations, but are understudied outside of rare disorders. 13 , 14 , 15 , 16 , 17 While recent efforts have resulted in the characterization of bi-allelic variation in large-scale population cohorts, researchers have so far been unable to systematically link CH variants to disease. 18 , 19…”

Exome-wide evidence of compound heterozygous effects across common phenotypes in the UK Biobank

“…CH disease associations have mainly been explored in rare disorders [13][14][15][16][17] , but are seldom investigated in the study of common disease. This is due to the low prevalence of variants in the CH state and the genetic architecture of common complex traits, which are typically influenced by environmental factors and numerous loci with low to modest contribution to risk.…”

“…Large-scale studies of bi-allelic damaging variation have generally been restricted to homozygotes in populations with excess homozygosity, such as Icelanders 9 , Finns 10,11 , and consanguineous populations 12 . In contrast, CH are expected to be more common in outbred populations, but are largely under-studied outside of rare disorders [13][14][15][16][17] .…”