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

RESULTS

In the 263 patients with NSHI, a total of 20 types of sequence changes were detected. These included 15 published mutations in GenBank, of which 10 were known pathogenic mutations (G4D, R32C, 35delG, E47X, W77X, 176-191del16, Q80R, 235delC, S139N and 299-300 delAT), five were previously described polymorphisms (T18I, T86R, G160S, Y38C and 50N) and five were novel sequence variations located in a highly conserved region. Table 1 lists the variations and number of affected alleles. Rates of Pathological Mutations in Individuals with NSHI. Of the 263 NSHI patients, 49 (18.6%) exhibited a GJB2 gene mutation: 29 cases were homozygous for a mutation, eight had compound heterozygous mutations and 12 had a single heterozygous mutation (Table 2). The types of mutation included 235delC, 176del6bp, 512insAACG, and 299delAT; 235delC was the most common type of GJB2 gene mutation, occurring in a total of 42 cases, 30 of whom were homozygous and the other 12 were heterozygous. Thirty patients (11.4%) carried mtDNA mutations; 28 cases had the C1494T mutation and two cases had the A1555G mutation. Mutation Status Differs with Age of Patient at First Hospital Visit. Patients were categorized by age at the ENT Department visit (Figure 1, Table 3), resulting in 67 adults and 196 pediatric cases (72 infants, 54 preschool cases, and 70 school-age cases). The GJB2 gene mutations were detected in 5.97% adults and 22.96% pediatric cases; this difference was statistically significant (χ2 = 9.506, p = 0.002). In contrast, mtDNA A1555G/C1494T mutations were detected in 31.34% adults and 4.59% pediatric cases; this difference was also statistically significant (χ2 = 35.359, p <0.001). Within the pediatric group, the distributions of both GJB2 gene and mtDNA mutations among the subcategories were statistically similar (each p value >0.05). Mutation Status Differs with Age of Onset of Deafness. Patients were divided by age of onset of NSHI, resulting in 26 adult cases and 237 pediatric cases (186 infants, 21 preschool cases, and 30 schoolage cases) (Figure 2, Table 4). The GJB2 gene mutations were not detected in any of the adult-onset cases, but were present in 20.68% of pediatric cases; this difference was statistically significant (p = 0.006). In contrast, mtDNA A1555G/C1494T mutations were detected in 15.38% of adult-onset patients and 8.86% of pediatric cases; this difference was not statis-tically significant (p = 0.288). Differences in mutation distributions in the pediatric subcategories were not statistically significant for either the GJB2 gene or mtDNA A1555G/C1494T mutations (each p value >0.05). For the pediatric cases, hearing loss was further classified as either pre-lingual or post-lingual (Table 5). The difference in GJB2 gene mutation between these two groups was statistically significant (χ2 = 4.683, p = 0.031); in contrast, the difference in mtDNA A1555G/C1494T mutations between these groups was not statistically significant (χ2 = 0.695, p = 0.404). Age Distributions Differ Between NSHI Patients with GJB2 Gene Mutations and Those with mtDNA Mutations. Patients who were positive for any mutation were subdivided into three age categories by mutation status and age of onset (Table 6). Patients with the GJB2 gene mutation primarily experienced onset within the first year of life (65.31%). Those with mtDNA A1555G/ C1494T mutations were nearly evenly divided between the three onset age groups. However, the difference in onset age distributions between those with GJB2 gene mutations and those with mtDNA mutations was statistically significant (p <0.05). Hearing Loss Phenotypes Differ by Mutation Status. Finally, patients were categorized according to their hearing loss phenotypes and mutation status. Patients with mtDNA A1555G/C1494T mutations generally exhibited mild-to-moderate hearing loss. In contrast, most patients with GJB2 gene mutations exhibited profound hearing loss. This difference in phenotypic distributions was statistically significant (p <0.05) (Table 7). Of the 30 patients with mtDNA A1555G/C1494T mutations, 22 underwent complete PTA. Severity of hearing loss was again judged according to the multiple grading standards: published recommendations [11], ISO-1964 criteria, and ISO- 1997 criteria, as well as the mean hearing thresholds at 0.25-8.0 kHz (full frequency band), 1.0-4.0 kHz and 4.0-8.0 kHz (Table 8). The difference between hearing loss judged according to the ISO-1964 criteria and the one judged according to the mean hearing threshold at 4.0-8.0 kHz, was statistically significant (p <0.001); however, the differences between hearing loss judged according to the mean hearing threshold at 4.0-8.0 kHz and the one according to the other criteria were not statistically significant (each p value >0.05).

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