Balkan Journal of Medical Genetics

GENETIC AND CLINICAL ANALYSIS OF NONSYNDROMIC HEARING IMPAIRMENT IN PEDIATRIC AND ADULT CASES
Xing J, Liu X, Tian Y, Tan J, Zhao H
*Corresponding Author: Mr. Xinguo Liu, Ear, Nose and Throat Department, The Central Hospital of Zhumadian, No. 747, Zhonghua Road, Zhumadian City, Henan Province, People’s Republic of China, 463000. Tel: +86-396-292-6205. Fax: +86-396-272-6530. E-mail: xingglsci@163.com
page: 35

DISCUSSION

Genetic diagnosis can help determine the etiology of NSHI for most patients with genetic deafness. The GJB2 gene mutation is the most common cause of genetic deafness of nuclear origin. In this study, the GJB2 gene mutation was detected in 18.63% of cases, which was lower than the report from Gabriel et al. [14] (22.0%). The mutations included 235delC, 76dell6bp, 512insAACG, and 299delAT. The 235delC was most common, and comprised both the homozygous mutation and the compound heterozygous mutation. This finding supports a previous report that a heterozygous mutation of a GJB2 gene could cause deafness [15]. Furthermore, GJB2 gene mutations were more common in pediatric cases, both by age of onset and age of first hospital visit, than in adult cases. Interestingly, a GJB2 gene mutation was most common in cases of pre-lingual deafness, suggesting that a GJB2 gene mutation is a significant contributor to pre-lingual deafness in Chinese individuals. Moreover, the age of deafness onset in patients with GJB2 gene mutations was typically within the first year of life; therefore, clinicians should perform routine tests for GJB2 gene mutations in pediatric NSHI patients. The GJB2 gene encodes the gap junction-connexin 26 (CX26) protein [16]. The 235delC mutation encodes a defective CX26 that results in an ineffective gap junction disrupting potassium homeostasis in the inner ear, particularly of the Corti’s organ, which subsequently leads to sensorineural deafness [17]. The hot-spot of mtDNA A1555G/C1494T mutations is located at the highly conserved coding region of the 12S rRNA gene [18]. In this study, 11.41% cases had mtDNA A1555G/C1494T mutations, mostly comprising the C1494T mutation. The age of onset of hearing loss did not differ by mtDNAA1555G/ C1494T mutation status, suggesting that these mutations can result in congenital deafness or acquired progressive deafness. Thus, clinicians should perform genetic screening for newborns with a matrilineal history of deafness. Interestingly, the findings of this study also indicated that patients with mtDNA A1555G/C1494T mutations more often exhibit mild hearing loss, often with some residual hearing. In contrast, most patients with GJB2 gene mutations exhibited profound hearing loss. However, the findings suggest that progressive aggravation of deafness is caused by mtDNA A1555G/C1494T mutations. The 22 patients with mtDNA A1555G/C1494T mutations who underwent complete PTA had more distinguishable hearing loss phenotypes. Previous studies reported differences in the deafness phenotypes of matrilineal family members carrying A1555G/C1494T mutations, in which the age of onset, the severity of hearing loss, and the hearing threshold curves differed despite shared genotypes [19-21]. The grading results suggest that deaf patients can be more easily discovered earlier by judging the severity of hearing loss according to the mean hearing threshold at 4.0-8.0 kHz. Clinically, most matrilineal family members carrying mtDNA A1555G/C1494T mutations have no self-felt hearing loss, but hearing tests can show that the high frequency decreases, and the low frequency and the stages of speech development are mostly normal. Therefore, when judging the severity of hearing loss in patients, clinicians should pay attention to the hearing frequency at 4.0-8.0 kHz and perform genetic susceptibility testing for those with decreased highfrequency hearing. In summary, a GJB2 gene mutation typically results in congenital deafness, while mtDNA A1555G/ C1494T mutations can result in congenital deafness or acquired and progressive deafness. Thus, newborn hearing screening combined with genetic screening is of great significance for early discovery, and appropriate interventions, for genetic deafness. Declaration of Interest. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

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