Effects of the GJB2 Gene c.109G>A (p.V37I) and c.235delC mutations on hearing function of Taiwanese hearing loss population

• Main Authors: Lin, Yi-Feng, 林宜鋒
• Other Authors: Hsu, Yi-Chao
• Format: Others
• Language: en_US
• Published: 2019
• Online Access: http://ndltd.ncl.edu.tw/handle/3uym4n

碩士 === 馬偕醫學院 === 生物醫學研究所 === 107 === Hearing loss is the most common abnormality in the sensory system and usually caused by the death or damage of inner ear hair cells. The damage or loss of hair cells may be caused by genetic mutations, aging, noise exposure, ototoxic drugs or bacterial and viral infections. No matter the etiology of hearing loss, symptoms on the pa tients are including hearing the wrong words, difficulty in receiving high frequency sounds, often asking the other person to repeat again, hard to communicate in noisy environments, loud voices, tinnitus or brain noise. These symptoms significantly reduce the quality of life of the hearing loss patients. Genetic mutation is one of the main causes of hearing loss. The prevalence of congenital genetic sensorineural hearing loss in Taiwan is about 3 5/1000, and about 2/3 of them are genetic mutations. The m ost common three sensory gene mutations in Taiwanese sensory neurological hearing loss are GJB2 , SLC26A4 and mitochondrial 12SrRNA. This study mainly focuses on the hearing loss caused by the two most common GJB2 c.109G>A (p.V37I) and c.235delC genes in T aiwanese population, and we analyze the hearing loss severity by analyzing the hearing function of patients with congenital hearing loss. In addition, we also try to discuss the role of these two GJB2 mutations in the auditory system. In this study, we extracted the DNA from the deaf patients’oral mucosa and performing Q-PCR genotyping assays to confirm their genotype, there were 58 patients with the mutations mentioned above found from the genetic screening of 240 hearing loss patients. There were 34 patients (25 GJB2 c.109G>A; 9 GJB2 c.235delC) with a total of GJB2 mutations after excluding the elder patients (above 10 years-old) that may be caused by age related degeneration. We found that the hearing loss levels in patients with GJB2 c.235delC homozygous mutation (Left ear: 80.8 ± 8.40 dB HL ; Right ear: 91.7 ± 5.40 dB HL) are significantly higher than the levels in the patients with GJB2 c.109G>A homozygous mutation (Left ear: 56.0 ± 3.60 dB HL ; Right ear: 54.5 ± 4.0 dB HL); GJB2c.109G>A heterozygous mutation (Left ear: 93.3 ± 5.60 dB HL ; Right ear: 80.7 ± 7.10 dB HL) are similar to the levels in the patients with GJB2 c.235delC heterozygous mutation (Left ear: 76.7 ± 20.9 dB HL ; Right ear: 76.7 ± 24.0 dB HL); The hearing levels in the patients with GJB2 c.235delC homozygous mutation (Left ear: 80.8 ± 8.4 0 dB HL ; Right ear: 91.7 ± 5.4 0 dB HL) are similar to the levels in the patients with GJB2 c.235delC heterozygous mutation (Left ear: 76.7 ± 20.90 dB HL ; Right ear: 76.7 ± 24.0 dB HL). The hearing levels in the patients with GJB2 c.109G> A heterozygous mutation (Left ear: 93.3 ± 5.60 dB HL ; Right ear: 80.7 ± 7.10 dB HL) is significantly higher than the levels in the patients with GJB2 c.109G>A homozygous mutation (Left ear: 56.0 ± 3.60 dB HL ; Right ear : 54.5 ± 4.0 dB HL). Based on the above results, this study provides a deeper understanding of the degree of hearing loss caused by GJB2 c.235delC and c.109G>A mutations, and we found the relevance of homozygous and heterozygous mutations of GJB2 gene in the hearing of deaf patients. Although we provide the interesting observations regarding the GJB2 heterozygous/homozygous mutations and the hearing levels, the underlying mechanisms require more studies to elucidate in the future.