Prevalence of Gene Mutations Correlated to Presence of Clinical and Environmental Risk Factors in the Etiology of Congenital Sensorineural Hearing Loss of the Romanian Population

Overview

Journal Exp Ther Med

Specialty Pathology

Date 2021 May 3

PMID 33936269

Citations 8

Authors

Alexandra Neagu

Adela-Ioana Mocanu

Alexandru Bonciu

Gabriella Coada

Horia Mocanu

Affiliations

Soon will be listed here.

Abstract

Although etiologically heterogeneous at least 50% of all early on-set hearing losses have a genetic cause and of these, the large majority, 75-80% are most probably autosomal recessive and 70% are non-syndromic. The rest of the congenital hearing losses are determined by clinical and environmental factors such as ototoxic medication, prematurity, and complications at birth. During the last decade it became clear that 50-80% of all such afflictions result from mutations in a single gene, , which encodes the protein Connexin 26. In order to, at least partially clarify this problem, especially in an emerging country such as Romania, where the problem is not studied adequately, we developed a comprehensive study of genetic, clinical and environmental risk factors for congenital hearing loss. The two most common variations of this gene, and in children with positive diagnosis of bilateral severe to profound sensorineural hearing loss were investigated. A cohort of 34 children (20 female and 14 male), ages between 2 and 10 (mean age 4.62 years), coming from 33 non-related families were evaluated. All cases were diagnosed with severe or profound bilateral congenital SNHL. A statistical comparison of genetic and environmental/clinical prevalence was also attempted since the presence of a genetic disorder cannot rule out the role of other documented risk factors in the etiology of SNHL. The results showed that, 29.4% of cases (10/34) were homozygotic for the mutation ), also known as genotype Δ/Δ. 5.88% of cases (2/34) belong to the heterozygotic bi-genic group . The clinical factors with high statistical significance for SNHL in a non-genetic group have no significance for genetic SNHL patients. Thus, the present study confirms the relatively high prevalence of the and mutations in cases of congenital non-syndromic severe of profound bilateral SNHL.

Citing Articles

Burden of rare genetic disorders in India: twenty-two years' experience of a tertiary centre.

Sheth J, Nair A, Sheth F, Ajagekar M, Dhondekar T, Panigrahi I Orphanet J Rare Dis. 2024; 19(1):295.

PMID: 39138584 PMC: 11323464. DOI: 10.1186/s13023-024-03300-z.

Materials for ossicular chain reconstruction: History and evolution (Review).

Mocanu H, Mocanu A, Dascalu I, Schipor M, Radulescu M Med Int (Lond). 2023; 3(2):13.

PMID: 36875817 PMC: 9982808. DOI: 10.3892/mi.2023.73.

Non-Syndromic Hearing Loss in a Romanian Population: Carrier Status and Frequent Variants in the Gene.

Riza A, Alkhzouz C, Farcas M, Pirvu A, Miclea D, Mihut G Genes (Basel). 2023; 14(1).

PMID: 36672810 PMC: 9858611. DOI: 10.3390/genes14010069.

Rare Gene Mutations in Romanian Hypoacusis Patients: Case Series and a Review of the Literature.

Neagu A, Budisteanu M, Gheorghe D, Mocanu A, Mocanu H Medicina (Kaunas). 2022; 58(9).

PMID: 36143929 PMC: 9501263. DOI: 10.3390/medicina58091252.

Rare and unusual benign tumors of the sinonasal tract and pharynx: Case series and literature review.

Mocanu H, Mocanu A, Moldovan C, Soare I, Postolache P, Nechifor A Exp Ther Med. 2022; 23(5):334.

PMID: 35401795 PMC: 8987923. DOI: 10.3892/etm.2022.11263.

References

Gasparini P, Rabionet R, Barbujani G, Melchionda S, Petersen M, Brondum-Nielsen K . High carrier frequency of the 35delG deafness mutation in European populations. Genetic Analysis Consortium of GJB2 35delG. Eur J Hum Genet. 2000; 8(1):19-23. DOI: 10.1038/sj.ejhg.5200406. View

Palmer C, Lueddeke J, Zhou J . Factors influencing parental decision about genetics evaluation for their deaf or hard-of-hearing child. Genet Med. 2009; 11(4):248-55. PMC: 2822638. DOI: 10.1097/GIM.0b013e318195aad9. View

Schimmenti L, Martinez A, Fox M, Crandall B, Shapiro N, Telatar M . Genetic testing as part of the early hearing detection and intervention (EHDI) process. Genet Med. 2004; 6(6):521-5. DOI: 10.1097/01.gim.0000144187.21727.28. View

Bitner-Glindzicz M . Hereditary deafness and phenotyping in humans. Br Med Bull. 2002; 63:73-94. DOI: 10.1093/bmb/63.1.73. View

Zelante L, Gasparini P, Estivill X, Melchionda S, DAgruma L, Govea N . Connexin26 mutations associated with the most common form of non-syndromic neurosensory autosomal recessive deafness (DFNB1) in Mediterraneans. Hum Mol Genet. 1997; 6(9):1605-9. DOI: 10.1093/hmg/6.9.1605. View

Grifa A, Wagner C, DAmbrosio L, Melchionda S, Bernardi F, Lopez-Bigas N . Mutations in GJB6 cause nonsyndromic autosomal dominant deafness at DFNA3 locus. Nat Genet. 1999; 23(1):16-8. DOI: 10.1038/12612. View

Lazar C, Popp R, Trifa A, Mocanu C, Mihut G, Al-Khzouz C . Prevalence of the c.35delG and p.W24X mutations in the GJB2 gene in patients with nonsyndromic hearing loss from North-West Romania. Int J Pediatr Otorhinolaryngol. 2010; 74(4):351-5. DOI: 10.1016/j.ijporl.2009.12.015. View

Al-Achkar W, Moassass F, Al-Halabi B, Al-Ablog A . Mutations of the Connexin 26 gene in families with non-syndromic hearing loss. Mol Med Rep. 2011; 4(2):331-5. DOI: 10.3892/mmr.2011.428. View

Pandya A, Arnos K, Xia X, Welch K, Blanton S, Friedman T . Frequency and distribution of GJB2 (connexin 26) and GJB6 (connexin 30) mutations in a large North American repository of deaf probands. Genet Med. 2003; 5(4):295-303. DOI: 10.1097/01.GIM.0000078026.01140.68. View

10.

Shahin H, Walsh T, Sobe T, Lynch E, King M, Avraham K . Genetics of congenital deafness in the Palestinian population: multiple connexin 26 alleles with shared origins in the Middle East. Hum Genet. 2002; 110(3):284-9. DOI: 10.1007/s00439-001-0674-2. View

11.

Nogueira C, Coutinho M, Pereira C, Tessa A, Santorelli F, Vilarinho L . Molecular investigation of pediatric portuguese patients with sensorineural hearing loss. Genet Res Int. 2012; 2011:587602. PMC: 3335713. DOI: 10.4061/2011/587602. View

12.

Withrow K, Burton S, Arnos K, Kalfoglou A, Pandya A . Consumer motivations for pursuing genetic testing and their preferences for the provision of genetic services for hearing loss. J Genet Couns. 2008; 17(3):252-60. DOI: 10.1007/s10897-007-9143-y. View

13.

. Worldwide survey of the delta F508 mutation--report from the cystic fibrosis genetic analysis consortium. Am J Hum Genet. 1990; 47(2):354-9. PMC: 1683705. View

14.

RamShankar M, Girirajan S, Dagan O, Ravi Shankar H, Jalvi R, Rangasayee R . Contribution of connexin26 (GJB2) mutations and founder effect to non-syndromic hearing loss in India. J Med Genet. 2003; 40(5):e68. PMC: 1735461. DOI: 10.1136/jmg.40.5.e68. View

15.

Wilcox S, Osborn A, Dahl H . A simple PCR test to detect the common 35delG mutation in the connexin 26 gene. Mol Diagn. 2000; 5(1):75-8. DOI: 10.1054/MODI00500075. View

16.

Boulay A, Del Castillo F, Giraudet F, Hamard G, Giaume C, Petit C . Hearing is normal without connexin30. J Neurosci. 2013; 33(2):430-4. PMC: 6704917. DOI: 10.1523/JNEUROSCI.4240-12.2013. View

17.

Cordeiro-Silva M, Barbosa A, Santiago M, Provetti M, Rabbi-Bortolini E . Prevalence of 35delG/GJB2 and del (GJB6-D13S1830) mutations in patients with non-syndromic deafness from a population of Espírito Santo-Brazil. Braz J Otorhinolaryngol. 2010; 76(4):428-32. PMC: 9446172. View

18.

Duncan R, Prucka S, Wiatrak B, Smith R, Robin N . Pediatric otolaryngologists' use of genetic testing. Arch Otolaryngol Head Neck Surg. 2007; 133(3):231-6. DOI: 10.1001/archotol.133.3.231. View

19.

Maheshwari M, Vijaya R, Ghosh M, Shastri S, Kabra M, Menon P . Screening of families with autosomal recessive non-syndromic hearing impairment (ARNSHI) for mutations in GJB2 gene: Indian scenario. Am J Med Genet A. 2003; 120A(2):180-4. DOI: 10.1002/ajmg.a.20014. View

20.

Neudert M, Bornitz M, Mocanu H, Lasurashvili N, Beleites T, Offergeld C . Feasibility Study of a Mechanical Real-Time Feedback System for Optimizing the Sound Transfer in the Reconstructed Middle Ear. Otol Neurotol. 2018; 39(10):e907-e920. DOI: 10.1097/MAO.0000000000002029. View