Role of <i>GJB2</i> and <i>GJB6</i> in Iranian Nonsyndromic Hearing Impairment: From Molecular Analysis to Literature Reviews

Falah, Masoumeh; Houshmand, Massoud; Balali, Maryam; Asghari, Alimohamad; Bagher, Zohreh; Alizadeh, Rafieh; Farhadi, Mohammad

doi:10.1080/15513815.2019.1627625

Cited by 14 publications

(15 citation statements)

References 47 publications

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“…Connexin26 and Connexin 30 are predominant isoforms in the cochlea (Zhao et al, 2006). Deletions in GJB6 are also common genetic factors for NSHL in some populations, with ethnic specificity (del Castillo et al, 2002;Marlin et al, 2005;Falah et al, 2020). Cases with digenic heterozygous mutations in GJB2 and GJB6 are relatively rare in the NSHL population, with various phenotypes, such as prelingual or post-lingual, ranging from mild or moderate to severe or profound hearing loss (Bolz et al, 2004;Cama et al, 2009;Chan et al, 2010;del Castillo and del Castillo, 2011;Mei et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Phenotypic Heterogeneity of Post-lingual and/or Milder Hearing Loss for the Patients With the GJB2 c.235delC Homozygous Mutation

Wang

Gao

Guan

et al. 2021

Front. Cell Dev. Biol.

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ObjectiveTo report the phenotypic heterogeneity of GJB2 c.235delC homozygotes associated with post-lingual and/or milder hearing loss, and explore the possible mechanism of these unconditional phenotypes.MethodsMutation screening of GJB2 was performed on all ascertained members from Family 1006983 and three sporadic patients by polymerase chain reaction (PCR) amplification and Sanger sequencing. Next generation sequencing (NGS) was successively performed on some of the affected members and normal controls from Family 1006983 to explore additional possible genetic codes. Reverse transcriptase–quantitative PCR was conducted to test the expression of Connexin30.ResultsWe identified a Chinese autosomal recessive hearing loss family with the GJB2 c.235delC homozygous mutation, affected members from which had post-lingual moderate to profound hearing impairment, and three sporadic patients with post-lingual moderate hearing impairment, instead of congenital profound hearing loss. NGS showed no other particular variants. Overexpression of Connexin30 in some of these cases was verified.ConclusionPost-lingual and/or moderate hearing impairment phenotypes of GJB2 c.235delC homozygotes are not the most common phenotype, revealing the heterogeneity of GJB2 pathogenic mutations. To determine the possible mechanism that rescues part of the hearing or postpones onset age of these cases, more cases are required to confirm both Connexin30 overexpression and the existence of modifier genes.

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Section: Introductionmentioning

confidence: 99%

Phenotypic Heterogeneity of Post-lingual and/or Milder Hearing Loss for the Patients With the GJB2 c.235delC Homozygous Mutation

Wang

Gao

Guan

et al. 2021

Front. Cell Dev. Biol.

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“…Over the last decade, a series of studies have been conducted on the Iranian population to identify the mutation spectrum and prevalence of GJB2 mutations (Azadegan‐Dehkordi et al., ; Falah et al., ; Hashemzadeh‐Chaleshtori et al., ; Hosseinipour et al., ; Koohiyan & Ahmadi, ; Mahdieh, Mahmoudi, Ahmadzadeh, & Bakhtiyari, ; Sadeghi et al., ). The diverse ethnicities, coupled with the high rate of consanguinity rates (38% in average) (Saadat, ), tend to change mutation frequencies among ethnic groups (Mahdieh et al., ; Sloan‐Heggen et al., ).…”

Section: Introductionmentioning

confidence: 99%

GJB2‐related hearing loss in central Iran: Review of the spectrum and frequency of gene mutations

Koohiyan

Koohian

Azadegan‐Dehkordi

2019

Annals of Human Genetics

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Mutations in the GJB2 gene are a main cause of autosomal-recessive nonsyndromic hearing loss (ARNSHL) in many populations. Previous studies have estimated the average frequency of GJB2 mutations to be ∼16% in Iran, but would vary among different ethnic groups. Here, we have taken together and reviewed results from our two previous publications and data from searching other published mutation reports to provide a comprehensive collection of data for GJB2 mutations and HL in central Iran. In all, 332 unrelated families were included and analyzed for the prevalence and type of the GJB2 gene mutations. In total, the frequency of GJB2 mutations was found to be 16% in the central provinces, which is significantly higher than those identified in southern populations of Iran. Also, c.35delG was the most frequent mutation in the related population. The present study suggests that mutations in the GJB2 gene, especially c.35delG, are important causes of HL in central Iran and can be used as a basis of genetic counseling and clinical guidelines in this region.

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“…Four novel variants, not previously reported in mitomap or the mtDB database, were identified in the control subjects and were submitted to mitomap. These variants were 96 C>A (previously reported as 96 C>T),19 15,864 A>G,20 15,906 A>T (previously reported as 15,906 A>C),21 and 16,046 T>G (previously reported as 16,046 T>C) 22…”

Section: Resultsmentioning

confidence: 89%

Association of genetic variations in the mitochondrial DNA control region with presbycusis

Falah¹,

Farhadi²,

Kamrava³

et al. 2017

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BackgroundThe prominent role of mitochondria in the generation of reactive oxygen species, cell death, and energy production contributes to the importance of this organelle in the intracellular mechanism underlying the progression of the common sensory disorder of the elderly, presbycusis. Reduced mitochondrial DNA (mtDNA) gene expression and coding region variation have frequently been reported as being associated with the development of presbycusis. The mtDNA control region regulates gene expression and replication of the genome of this organelle. To comprehensively understand of the role of mitochondria in the progression of presbycusis, we compared variations in the mtDNA control region between subjects with presbycusis and controls.MethodsA total of 58 presbycusis patients and 220 control subjects were enrolled in the study after examination by the otolaryngologist and audiology tests. Variations in the mtDNA control region were investigated by polymerase chain reaction and Sanger sequencing.ResultsA total of 113 sequence variants were observed in mtDNA, and variants were detected in 100% of patients, with 84% located in hypervariable regions. The frequencies of the variants, 16,223 C>T, 16,311 T>C, 16,249 T>C, and 15,954 A>C, were significantly different between presbycusis and control subjects.ConclusionThe statistically significant difference in the frequencies of four nucleotide variants in the mtDNA control region of presbycusis patients and controls is in agreement with previous experimental evidence and supports the role of mitochondria in the intracellular mechanism underlying presbycusis development. Moreover, these variants have potential as diagnostic markers for individuals at a high risk of developing presbycusis. The data also suggest the possible presence of changes in the mtDNA control region in presbycusis, which could alter regulatory factor binding sites and influence mtDNA gene expression and copy number.

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Role of GJB2 and GJB6 in Iranian Nonsyndromic Hearing Impairment: From Molecular Analysis to Literature Reviews

Cited by 14 publications

References 47 publications

Phenotypic Heterogeneity of Post-lingual and/or Milder Hearing Loss for the Patients With the GJB2 c.235delC Homozygous Mutation

Phenotypic Heterogeneity of Post-lingual and/or Milder Hearing Loss for the Patients With the GJB2 c.235delC Homozygous Mutation

GJB2‐related hearing loss in central Iran: Review of the spectrum and frequency of gene mutations

Association of genetic variations in the mitochondrial DNA control region with presbycusis

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