Putative Digenic GJBI2/MYO7A Inheritance of Hearing Loss Detected in a Patient with 48, XXYY Klinefelter Syndrome

Abstract

Background: 48, XXYY Klinefelter syndrome is a rare sex chromosome abnormality. Nonsyndromic hearing loss (NSHL) is the most frequent hereditary type of hearing impairment. There has been no report of NSHL combined with 48XXYY. The purpose of this study was to explore the underlying genetic cause in a three-generation family affected by NSHL. The proband had concomitant NSHL and 48, XXYY syndrome. The whole-exome sequencing was performed in the proband. The candidate pathogenic variants identified by whole-exome sequencing were then confirmed by Sanger sequencing and segregation analysis.Results: The proband was identified to be compound heterozygous for c.109G>A (p.V37I) variant in the GJB2 gene and additional heterozygous for the c.1039C>A (p.L347I) variants in the MYO7A gene. His mother had normal hearing and did not have any form of variant. His father and uncle, both had NSHL, were digenic compound heterozygote for the GJB2 p.V37I and MYO7A p.L347I variants, thus suggesting a possible GJB2/MYO7A digenic inheritance of NSHL in this family consist with the clinical phenotype.Conclusions: Our findings reported a putative GJB2/MYO7A digenic inheritance form of hearing loss, which expands the mutation spectrum of NSHL. This is also the first report of concomitant NSHL and 48, XXYY syndrome.