Analysis of GJB2 mutations and the clinical manifestation in a large Hungarian cohort

Kecskeméti, Nóra; Szőnyi, Magdolna; Gáborján, Anita; Küstel, Marianna; Milley, Gyorgy Mate; Süveges, Anna; Illés, Anett; Kékesi, Anna; Tamás, László; Molnár, Mária Judit; Szirmai, Ágnes; Gál, Anikó

doi:10.1007/s00405-018-5083-4

Cited by 14 publications

(12 citation statements)

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“…Genetic diagnosis was confirmed in 174 (59.7%) of the 291 patients with different degrees of hearing impairment, most of them being accounted for GJB2 gene. This data is in accordance with the literature, GJB2 mutations are frequent in all studied populations [13,14,[33][34][35][36][37][38]. In some populations GJB2 mutations are prevalent due to consanguineous marriages.…”

Section: Discussionsupporting

confidence: 93%

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

Resmerita

Cozma

Popescu

et al. 2020

Genes

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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.

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Section: Discussionsupporting

confidence: 93%

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

Resmerita

Cozma

Popescu

et al. 2020

Genes

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“…GJB2 mutation is a major cause of hereditary NSHL, and most mutations are located in the coding region [49]. Up to 50% of cases of autosomal recessive NSHL are attributable to GJB2 mutation in many populations worldwide [29,30]. Therefore, genetic testing for GJB2 mutations is a primary screening process for the molecular diagnosis of HL.…”

Section: Discussionmentioning

confidence: 99%

“…Notably, several alleles have been found to be particularly enriched in certain populations: c.35delG in Europe, America, North Africa, and the Middle East; c.71G>A in India and Pakistan; c.167delT in Ashkenazi Jews; and c.109G>A in East and Southeast Asia [ 16 , 26 – 28 ]. The contribution of GJB2 mutations to genetic HL varies by ethnicity, but such mutations are the primary cause of congenital severe-to-profound autosomal recessive NSHL (up to 50% worldwide) [ 29 , 30 ]. In addition, mild and moderate HL are associated with GJB2 common mutations such as c.35delG and c.109G>A, showing diverse hearing phenotypes [ 31 , 32 ].…”

Section: Introductionmentioning

confidence: 99%

Hearing Phenotypes of Patients with Hearing Loss Homozygous for the GJB2 c.235delc Mutation

et al. 2020

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Hereditary hearing loss is characterized by remarkable phenotypic heterogeneity. Patients with the same pathogenic mutations may exhibit various hearing loss phenotypes. In the Chinese population, the c.235delC mutation is the most common pathogenic mutation of GJB2 and is closely related to hereditary recessive hearing loss. Here, we investigated the hearing phenotypes of patients with hearing loss associated with the homozygous c.235delC mutation, paying special attention to asymmetric interaural hearing loss. A total of 244 patients with the GJB2 c.235delC homozygous mutation encountered from 2007 to 2015 were enrolled. The severity of hearing loss was scaled with the American Speech-Language-Hearing Association (ASHA). Auditory phenotypes were analyzed, and three types of interaural asymmetry were defined based on audiograms: Type A (asymmetry of hearing loss severity), Type B (asymmetry of audiogram shape), and Type C (Type A plus Type B). Of the 488 ears (244 cases) examined, 71.93% (351) presented with profound hearing loss, 14.34% (70) with severe hearing loss, and 9.43% (46) with moderate to severe hearing loss. The most common audiogram shapes were descending (31.15%) and flat (24.18%). A total of 156 (63.93%) of the 244 patients exhibited asymmetric interaural hearing loss in terms of severity and/or audiogram shape. Type A was evident in 14 of these cases, Type B in 106, and Type C in 36. In addition, 211 of 312 ears (67.63%) in the interaural hearing asymmetry group showed profound hearing loss, and 59 (18.91%) exhibited severe hearing loss, with the most common audiogram shapes being flat (27.88%) and descending (22.12%). By contrast, in the interaural hearing symmetry group, profound hearing loss was observed in 140 ears (79.55%), and the most common audiograms were descending (46.59%) and residual (21.59%). Hearing loss associated with the GJB2 c.235delC homozygous mutation shows diverse phenotypes, and a considerable proportion of patients show bilateral hearing loss asymmetry.

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“…Ez a mutáció Európában a leggyakoribb patogén eltérés, homozigótahordozás esetén súlyos fokú halláscsökkenés, míg compound heterozigóta formában a halláscsökkenés széles spektruma alakulhat ki [17]. Korábbi tanulmányunkban, melynek során felnőtt és gyermek, kisfokútól súlyos fokig terjedő halláscsökkenéssel rendelkező betegek körében vizsgáltuk a különböző mutációk előfordulása és klinikai megjelenésük közötti összefüggést, csak 12,6%-os c.35delG-allélfrekvenciát találtunk [18]. Jelen vizsgálatunk rámutat, hogy a súlyos fokú halláscsökkent betegek között nagy találati eredményt kapunk, így ezt a genetikai vizsgálatot elsősorban ebben a betegpopulációban érdemes elvégezni.…”

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Halláscsökkenést okozó etiológiai tényezők cochlearis implantáción átesett gyermekekben

et al. 2019

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Introduction: Congenital sensorineural hearing loss is one of the most common sensory defects affecting 1–3 children per 1000 newborns. There are a lot of causes which result in congenital hearing loss, the most common is the genetic origin, but infection, cochlear malformation or other acquired causes can be reasons as well. Aim: The aim of this study was to establish the etiological factors of congenital profound sensorineural hearing loss in children who underwent cochlear implantation. Results: Our results show that the origin of the hearing loss was discovered in 62.9% of our patients. The most common etiological factor was the c.35delG mutation of the gap junction protein β-2 gene, the allele frequency was 38.7% in our cohort. Infection constituted to 10.1%, and meningitis and cytomegalovirus infection were the second most common cause. 79.9% of our patients received sufficient hearing rehabilitation before the end of the speech development’s period (6 years old), but 11.2% of our cases were still diagnosed late. Conclusions: Based on our data we can state that genetic evaluation is crucial in the diagnostic process of congenital profound sensorineural hearing loss. Sufficient hearing rehabilitation affects the whole life of the child, and by late cochlear implantation the speech development falls behind. We can decrease the ratio of the late implantation with the new protocol of newborn hearing screening, and with sufficient information provided to the colleagues, so the children may be referred to the proper center for rehabilitation without delay. Orv Hetil. 2019; 160(21): 822–828.

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Analysis of GJB2 mutations and the clinical manifestation in a large Hungarian cohort

Cited by 14 publications

References 29 publications

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

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

Hearing Phenotypes of Patients with Hearing Loss Homozygous for the GJB2 c.235delc Mutation

Halláscsökkenést okozó etiológiai tényezők cochlearis implantáción átesett gyermekekben

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