Genetics of Hearing Impairment in North-Eastern Romania—A Cost-Effective Improved Diagnosis and Literature Review

Abstract

Background: We have investigated the main genetic causes for non-syndromic hearing impairment (NSHI) in the hearing impairment individuals from the North-Eastern Romania and proposed a cost-effective diagnosis protocol. Methods: MLPA followed by Sanger Sequencing were used for all 291 patients included in this study. Results: MLPA revealed abnormal results in 141 cases (48.45%): 57 (40.5%) were c.35delG homozygous, 26 (18.44%) were c.35delG heterozygous, 14 (9.93%) were compound heterozygous and 16 (11.35%) had other types of variants. The entire coding region of GJB2 was sequenced and out of 150 patients with normal results at MLPA, 29.33% had abnormal results: variants in heterozygous state: c.71G>A (28%), c.457G>A (20%), c.269T>C (12%), c.109G>A (12%), c.100A>T (12%), c.551G>C (8%). Out of 26 patients with c.35delG in heterozygous state, 38.46% were in fact compound heterozygous. Conclusions: We identified two variants: c.109G>A and c.100A>T that have not been reported in any study from Romania. MLPA is an inexpensive, rapid and reliable technique that could be a cost-effective diagnosis method, useful for patients with hearing impairment. It can be adaptable for the mutation spectrum in every population and followed by Sanger sequencing can provide a genetic diagnosis for patients with different degrees of hearing impairment.

Audiological features in Serbian patients with hearing impairment identified with c.35delG in the GJB2 gene

“…Among the patients eleven exhibited a profound degree of hearing loss with over Only two patients exhibited moderately severe degree of hearing impairment with ~60dB. Our results are in agreement with many published studies worldwide [18,19,25,26]. In general, the majority of homozygotes for the c.35delG exhibit severe to profound hearing impairment, while in a few rare cases develop moderate to even mild hearing impairment [2,3,7,8].…”

“…In the present study, the total frequency of the c.35delG mutant allele was estimated at 30.43% (56/184 alleles) and was identified in 37 patients either in homozygote or heterozygote state (40.22%) (Table 2). The recovered numbers concerning homozygosity and/or heterozygosity of the c35delG are quite similar to the ones previously reported in neighboring populations [10,[18][19][20][21][22][23][24] (Table 3).…”

“…In the group 2 of the present study were allocated 4 patients (4.35% of total cohort) with the compound heterozygous genotype, all of them demonstrated profound hearing loss (Table 2). Similar results were also found in compound heterozygotes from Romanian and Croatian populations identified in 4.8% and 7.9% of total cohort (respectively), who mostly exhibited profound degree of hearing impairment [18,19].…”

“…Nowadays, c.35delG mutation has been widely known as the most prevalent mutation in Caucasians either in the homozygous state or compound heterozygote state in GJB2 or GJB6 genes [4,11]. Since c.35delG is a truncating and frameshift mutation leads to premature protein synthesis termination at the 12 th amino acid [18]. In the present study, the total frequency of the c.35delG mutant allele was estimated at 30.43% (56/184 alleles) and was identified in 37 patients either in homozygote or heterozygote state (40.22%) (Table 2).…”

The Effectiveness of Cochlear Implantation for Children of Hereditary Deafness: A Multicenter Retrospective Study

“…Relevant epidemiological data show that the number of hearing disabilities in the world is as high as 360 million, accounting for 5.3% of the global population, including 32 million children [ 9 ]. This is the largest number of hearing-impaired children in the world, and the number of hearing-impaired children is increasing by 20,000 to 30,000 every year [ 10 , 11 ]. Hearing impairment will have a nonnegligible impact on the formation of language, which may cause developmental impairment or stagnation of language function and then affect the psychology, intelligence, and social communication ability of children [ 12 ].…”