Mutation in second exon of MYO15A gene cause of nonsyndromic hearing loss and its association in the Arab population in Iran

Hearing loss is a genetically and clinically heterogeneous defect and more than 140 loci and 65 genes have been identified to cause autosomal recessive non-syndromic hearing loss (ARNSHL). According to the previous studies, mutations in GJB2 are estimated to be involved in 18.17% of ARNSHL cases in the Iranian population; as a result, the remaining 81.83% of this disorder is yet ambiguous. This study aimed to determine the contribution of DFNB3 in hearing loss as well as the frequency of gene mutations in a population (Arab tribal origin) in the Southwest of Iran. In this descriptive laboratory study, we included 25 families from the Southwest of Iran and negative GJB2 gene. Linkage analysis was performed by DFNB3 (MYO15A) molecular markers (STR). The families with hearing loss linked to this locus were further analyzed for mutation detection. MYO15A gene exons were amplified and analyzed using direct DNA sequencing. In studied families, one family displayed linkage to DFNB3 locus. Identified mutations include substitution and substitute C for A in 1047 location of coding region of MYO15A gene (c.1047 C>A) in exon 2 which cause to change Tyrosin to stop codons (P.Y349X), results in the premature truncation at amino acid position 349.

Download Full-text

Gjb3 Gene Mutations in Non-Syndromic Hearing Loss of Bloch, Kurd, and Turkmen Ethnicities in Iran

Iranian Journal of Public Health ◽

10.18502/ijph.v49i11.4730 ◽

2020 ◽

Author(s):

Farnoush ALIAZAMI ◽

Dariush D. FARHUD ◽

Marjan ZARIF-YEGANEH ◽

Siamak SALEHI ◽

Azam HOSSEINIPOUR ◽

...

Keyword(s):

Hearing Loss ◽

Dna Sequencing ◽

Gene Mutations ◽

Sensorineural Deafness ◽

Heterozygous Mutation ◽

Coding Region ◽

Dominant Form ◽

Direct Dna Sequencing ◽

Junction Protein ◽

Syndromic Hearing Loss

Background: Hearing loss (HL) is one of the most common heterogeneous congenital disabilities worldwide. Gap junction protein β-3 (GJB3) gene encodes Connexin31 protein (Cx31). The hereditary type of hearing impairment in this gene are known to cause both autosomal recessive and autosomal dominant form. In addition, GJB3 mutations have been involved in sensorineural deafness, erythrokeratodermia variabilis (EKV), and neuropathy diseases. We aimed to investigate GJB3 mutations in people suffering from HL among three different ethnicities of Iranian population (Baloch, Kurd, and Turkmen). Methods: In this descriptive study, 50 GJB2-negative non-syndromic hearing loss (NSHL) Iranian individuals from 3 ethnic groups of Baloch (n=17), Kurd (n =15) and Turkmen (n=18) were enrolled. DNA extractions, PCR, and mutation detection was carried out for the two large deletions of the GJB6, del (GJB6 -D13S1830,) and del (GJB6 -D13S1854) followed by direct DNA sequencing method for the GJB3. Results: DNA sequencing of GJB3 was shown a missense heterozygous mutation rs199689484 (NM_024009.3) GJB3: c.340G>A (p.Ala114Thr) in a Baloch patient, and a polymorphism rs35983826 (NM_024009.3) GJB3: c.798C>T (p.Asn266=) in a Turkman patient, in coding region of the GJB3. We did not detect del (GJB6 -D13S1830) and del (GJB6 -D13S1854) among these three ethnicities in Iran. Conclusion: Deafness is a heterogeneous disorder. Specific genes and mutations contribute to hearing loss that varies from locus to locus as well as from population to population.

Download Full-text

Spectrum and frequencies of non GJB2 gene mutations in Czech patients with early non‐syndromic hearing loss detected by gene panel NGS and whole‐exome sequencing

Clinical Genetics ◽

10.1111/cge.13839 ◽

2020 ◽

Vol 98 (6) ◽

pp. 548-554

Author(s):

Dana Safka Brozkova ◽

Simona Poisson Marková ◽

Anna Uhrová Mészárosová ◽

Ján Jenčík ◽

Vlasta Čejnová ◽

...

Keyword(s):

Hearing Loss ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Gene Mutations ◽

Gene Panel ◽

Gjb2 Gene ◽

Whole Exome ◽

Syndromic Hearing Loss

Download Full-text

High frequency of heterozygosity in GJB2 mutations among patients with non-syndromic hearing loss

The Journal of Laryngology & Otology ◽

10.1017/s0022215108002892 ◽

2008 ◽

Vol 123 (3) ◽

pp. 273-277 ◽

Cited By ~ 5

Author(s):

G Khandelwal ◽

S Bhalla ◽

M Khullar ◽

N K Panda

Keyword(s):

Hearing Loss ◽

Indian Population ◽

Gjb2 Gene ◽

Coding Region ◽

Syndromic Hearing Loss ◽

Polymerase Chain ◽

35Delg Mutation ◽

Control Study ◽

Gjb2 Mutations ◽

Prevalent Mutation

AbstractObjective:To determine the prevalence of GJB2 mutations among subjects with congenital, non-syndromic, sensorineural hearing loss, within a north Indian population.Materials and methods:This was a case–control study in which the frequencies of the three most prevalent GJB2 mutations (35delG, W24X and 167delT) were studied. Polymerase chain reaction restriction fragment length polymorphism assays were performed to detect these mutations. The entire coding region of the GJB2 gene was sequenced in all patients, and also in any of their family members who showed GJB2 mutations.Results:The 35delG mutation was found to be the most prevalent mutation (21 per cent), followed by the W24X mutation (7 per cent). This is the first report of the 35delG mutation in an Indian population. One patient was a compound heterozygote for 35delG/W24X. The 167delT mutation was not observed in any patient.Conclusions:These findings challenge the classical view that the W24X variant of the GJB2 gene represents a single ‘founder’ mutation.

Download Full-text

Whole-Genome Sequencing Improves the Diagnosis of DFNB1 Monoallelic Patients

Genes ◽

10.3390/genes12081267 ◽

2021 ◽

Vol 12 (8) ◽

pp. 1267

Author(s):

Anaïs Le Nabec ◽

Mégane Collobert ◽

Cédric Le Maréchal ◽

Rémi Marianowski ◽

Claude Férec ◽

...

Keyword(s):

Hearing Loss ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Gjb2 Gene ◽

Whole Genome ◽

Genetic Origin ◽

Functional Assays ◽

Syndromic Hearing Loss ◽

Sensory Defect

Hearing loss is the most common sensory defect, due in most cases to a genetic origin. Variants in the GJB2 gene are responsible for up to 30% of non-syndromic hearing loss. Today, several deafness genotypes remain incomplete, confronting us with a diagnostic deadlock. In this study, whole-genome sequencing (WGS) was performed on 10 DFNB1 patients with incomplete genotypes. New variations on GJB2 were identified for four patients. Functional assays were realized to explore the function of one of them in the GJB2 promoter and confirm its impact on GJB2 expression. Thus, in this study WGS resolved patient genotypes, thus unlocking diagnosis. WGS afforded progress and bridged some gaps in our research.

Download Full-text

Genetics of non Syndromic Hearing Loss in the Republic of Macedonia

Balkan Journal of Medical Genetics ◽

10.2478/v10034-012-0020-0 ◽

2012 ◽

Vol 15 (Supplement) ◽

pp. 57-59 ◽

Cited By ~ 2

Author(s):

Emilija Sukarova Stefanovska ◽

D Plaseska Karanfilska ◽

M Cakar ◽

I Filipce

Keyword(s):

Hearing Loss ◽

Direct Sequencing ◽

Gene Mutations ◽

Developed Countries ◽

Deaf Children ◽

Mtdna Mutations ◽

Republic Of Macedonia ◽

Syndromic Hearing Loss ◽

The Republic ◽

Genetic And Environmental Factors

ABSTRACT Hearing impairment is the most common sensory deficit in humans affecting 1 in 1000 newborns. When present in an infant, deafness may have dramatic effects on language acquisition, seriously compromising the quality of their life. Deafness is influenced by both genetic and environmental factors, with inherited causes as the most prominent etiological factor in deafness in developed countries. The genetic basis of hearing loss is complex with numerous loci and genes underlying hereditary sensoryneural non syndromic hearing loss (NSHL) in humans. Despite the wide functional heterogeneity of the genes, mutations in the GJB2 gene are found to be the most common cause of sporadic and recessive NSHL in many populations worldwide. Molecular characterization of deafness in the Republic of Macedonia was performed in 130 NSHL profoundly deaf children from different ethnic origins. Molecular studies included direct sequencing of the GJB2 gene and specific polymerase chain reaction (PCR) analyses for the del(GJB6- D13S1830) mutation. Five common mitochondrial DNA (mtDNA) mutations [A1555G, 961delT+ C(n), T1095C, C1494T and A827G] were also analyzed using the SNaPShot method. In preliminary studies, GJB2 gene mutations were found in 36.4% of analyzed patients, with predominance of 35delG in Macedonian and Albanian patients and W24X in Gypsy patients, respectively. No del(GJB6- D13S1830) mutation was found. None of the analyzed deafness-associated mutations in mtDNA were identified in the studied patients

Download Full-text

Update of the spectrum of GJB2 gene mutations in Tunisian families with autosomal recessive nonsyndromic hearing loss

Gene ◽

10.1016/j.gene.2013.04.078 ◽

2013 ◽

Vol 525 (1) ◽

pp. 1-4 ◽

Cited By ~ 23

Author(s):

Zied Riahi ◽

Hassen Hammami ◽

Houyem Ouragini ◽

Habib Messai ◽

Rim Zainine ◽

...

Keyword(s):

Hearing Loss ◽

Autosomal Recessive ◽

Gene Mutations ◽

Gjb2 Gene ◽

Nonsyndromic Hearing Loss

Download Full-text

Mutations in the connexin26/GJB2 gene are the most common event in non-syndromic hearing loss among the German population

Human Mutation ◽

10.1002/humu.1138 ◽

2001 ◽

Vol 17 (6) ◽

pp. 521-522 ◽

Cited By ~ 59

Author(s):

Heinz Gabriel ◽

Petra Kupsch ◽

J�rgen Sudendey ◽

Elke Winterhager ◽

Klaus Jahnke ◽

...

Keyword(s):

Hearing Loss ◽

Gjb2 Gene ◽

German Population ◽

Common Event ◽

Syndromic Hearing Loss

Download Full-text

Connexin 26 Gene Mutations in Non-Syndromic Hearing Loss Among Kuwaiti Patients

Medical Principles and Practice ◽

10.1159/000348304 ◽

2014 ◽

Vol 23 (1) ◽

pp. 74-79 ◽

Cited By ~ 5

Author(s):

Khalid Al-Sebeih ◽

Marium Al-Kandari ◽

Sadika A. Al-Awadi ◽

Fatma F. Hegazy ◽

Ghada A. Al-Khamees ◽

...

Keyword(s):

Hearing Loss ◽

Gene Mutations ◽

Connexin 26 ◽

Syndromic Hearing Loss

Download Full-text

Spectrum and Frequency of the GJB2 Gene Mutations Among Latvian Patients with Prelingual Nonsyndromic Hearing Loss

Proceedings of the Latvian Academy of Sciences Section B Natural Exact and Applied Sciences ◽

10.2478/v10046-009-0031-8 ◽

2009 ◽

Vol 63 (4-5) ◽

pp. 198-203

Author(s):

Olga Šterna ◽

Natālija Proņina ◽

Ieva Grīnfelde ◽

Sandra Kušķe ◽

Astrīda Krūmiņa ◽

...

Keyword(s):

Hearing Loss ◽

Gene Mutations ◽

Gjb2 Gene ◽

Connexin 26 ◽

Compound Heterozygous ◽

Nonsyndromic Hearing Loss ◽

Profound Hearing Loss ◽

Common Cause ◽

Gjb2 Mutation ◽

35Delg Mutation

Spectrum and Frequency of the GJB2 Gene Mutations Among Latvian Patients with Prelingual Nonsyndromic Hearing Loss Mutations in the GJB2 gene (connexin 26) are the most common cause of congenital nonsyndromic severe-to-profound hearing loss. Sixty-five hearing impaired probands from Latvia were tested for mutations in the GJB2 gene to determine the percentage of hearing loss attributed to connexin 26 and the types of mutations in this population. A total of 62% of patients tested had GJB2 mutations. Four different mutations in the GJB2 gene were identified in Latvian patients with nonsyndromic sensorineural hearing loss: 35delG, 311-324del14, 235delC and M34T. The most prevalent mutation is 35delG (47% of all probands were homozygous and 8% compound heterozygous). Our findings support the conclusion that the 35delG mutation is the most prevalent GJB2 mutation and that it is the common cause of hereditary nonsyndromic hearing loss in populations of European descent.

Download Full-text