Initially, doctors assumed that my hearing loss was related to mutations in the connexin gene family. Nonsyndromic Hearing-Impairment is commonly mapped to 30 different genes. Out of the 30 genes, three related genes GJB2, 3, & 6 encode Connexin 26, 31, and 30, accounting for 50% of the nonsyndromic hearing population. It is known that a large percentage (10-50%) of nonsyndromic hearing loss patients carry one mutant allele. 11% carry one GJB2 (Connexin 26 / CX26) mutation, and a (del(GJB6-D1S1830)) deletion with one breakpoint inside the GJB6 (Connexin 30 / CX30) gene.
In 2010, the CX26 gene was analyzed by PCR amplifying highly purified genomic DNA, followed by automated unidirectional DNA sequencing of the coding region (2 exons, 867 GP) of the CX26 gene. 10 bases of intronic DNA surrounding each exon including the highly conserved flanking intronic sequences of the exon-intron splice junctions for all 2 exons were sequenced.
Athena Diagnostics did not identify any abnormal DNA sequence variants in the coding region, intron/exon junctions for CX26, or the common deletion in CX30. Therefore, they concluded that I was unlikely to be affected with, or predisposed to developing, nonsyndromic hearing impairment due to mutations in the CX26 and CX30 genes. However, they knew that this analysis did not definitively rule out nonsyndromic hearing impairment due to (1) mutations in another gene not yet identified/discovered, (2) mutations in regions of CX26 and CX300 that were not tested, and (3) mutations that are not detectable by the technology used in the assay.
In 2011, I undertook tests at the Stanford Clinical Laboratory. The Pendred Syndrome locus (SLC26A4) was tested for the presence of sequence variants by PCR followed by direct DNA sequencing of the 21 exons as well as surrounding noncoding regions. I was classified as heterozygous for two mutations in the SLC26A4 gene. The mutations are c.919-2A>G (splice site mutation) and p.Arg 409His (c.1226G>A) (missense mutation). Both are pathogenic mutations associated with Pendred Syndrome hearing loss when present in homozygous or compound heterozygous configurations. Considering the severity of my hearing loss, these two mutations are likely causative and in a compound heterozygous configuration. Later parent studies could confirm if these mutations are on the same or opposite chromosomes.
Below is an audiogram of the two extremas of my hearing loss.
Below is an audiogram of all of my hearing tests compiled together.
Due to the severity of my hearing loss, I wear Phonak Sky B90-UP hearing aids. While I was offered to undergo surgery for cochlear implantation, I have chosen to wear hearing aids to prevent possible surgical complications.