Diagnostic pitfalls for GJB2-related hearing loss: A novel deletion detected by Array-CGH analysis in a Japanese patient with congenital profound hearing loss

Abstract

Here, we report a novel deletion (copy number variation: CNV) in the GJB2 gene observed in a Japanese hearing loss patient. The deleted segment started in the middle of the GJB2 gene, but the GJB6 gene remained intact. This partial deletion in the GJB2 gene highlights the need for further improvements in GJB2 screening.

Keywords: CNV; GJB2 gene; novel deletion; profound hearing loss.

Figure 1

Pedigree and genomic DNA analysis. A, The audiograms of both ears in the proband of the family revealed profound hearing loss. Black triangles: the hearing threshold level via cochlear implant. B, Direct sequencing electropherograms of GJB2 showing the p.R143W homozygote in the patient. C, Agarose gel electrophoresis of the PCR products in this family. In the patient and her mother, p.R143W‐specific amplified bands are observed. PCR products for p.R143R_r allele‐specific and upstream designed primers were absent (red arrowhead) in the patient only. For the wild‐type sample, all the corresponding amplified PCR fragments were observed except for PCR amplification by p.R143W‐specific primers

Figure 2

Location of deletions at the DFNB1 locus on chromosome 13q12.11. A, Results of Array‐CGH for the GJB2 gene region in the patient. Hybridization results are shown for the affected patient in whom an abnormality was identified by Array‐CGH. For each panel, the x‐axis marks the distance, in megabases, along the chromosome from the q telomere. The y‐axis marks the hybridization ratio plotted on a log₂ scale. The patient shows a hemizygous deletion involving in the GJB2 gene region based on analysis using CytoGenomics software. The area shown in red is depleted by one copy loss. The upper panel includes the region up to GJB6, and the lower panel is an expanded image showing the approximate eight thousand base pair deletion. B, Schematic map of seven deletions. All genomic configurations are derived from NC_000013.11(Reference: GRCh38.p12 Primary Assembly)