A study of GJB2 and delGJB6-D13S1830 mutations in Brazilian non-syndromic deaf children from the Amazon region

Castro, Luciana Santos Serrao de; Marinho, Andrey Moacir do Rosário; Rodrigues, Elzemar Martins Ribeiro; Marques, Giorgio Christie Tavares; Carvalho, Tarcísio André Amorim de; Silva, Luiz Carlos Santana da; Santos, Sidney Emanuel Batista dos

doi:10.5935/1808-8694.20130016

Cited by 14 publications

(7 citation statements)

References 45 publications

(61 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For instance, the Northern region had a diagnostic rate of 7.7%, and c.35delG was the only pathogenic variant detected (Fig. 2D-F), in agreement with a study from the same region (Pará state) in which a diagnostic rate was 1.3% and c.35delG represented 80% of the mutated alleles, but GJB6 deletions were not tested (Castro et al 2013). Conversely, the other studies performed in the NE region were not comparable to ours because they included related patients (Manzoli et al 2013) or patients from a small geographical region (Melo et al 2014).…”

Section: Brazil's Regional Differences In Gjb2/gjb6 Contribution: Corroborating and Expanding Previous Studiessupporting

confidence: 90%

Molecular and genetic characterization of a large Brazilian cohort presenting hearing loss

et al. 2021

View full text Add to dashboard Cite

Hearing loss is one of the most common sensory defects, affecting 5.5% of the worldwide population and significantly impacting health and social life. It is mainly attributed to genetic causes, but their relative contribution reflects the geographical region's socio-economic development. Extreme genetic heterogeneity with hundreds of deafness genes involved poses challenges for molecular diagnosis. Here we report the investigation of 542 hearing-impaired subjects from all Brazilian regions to search for genetic causes. Biallelic GJB2/GJB6 causative variants were identified in 12.9% (the lowest frequency was found in the Northern region, 7.7%), 0.4% carried GJB2 dominant variants, and 0.6% had the m.1555A > G variant (one aminoglycoside-related). In addition, other genetic screenings, employed in selected probands according to clinical presentation and presumptive inheritance patterns, identified causative variants in 2.4%. Ear malformations and auditory neuropathy were diagnosed in 10.8% and 3.5% of probands, respectively. In 3.8% of prelingual/perilingual cases, Waardenburg syndrome was clinically diagnosed, and in 71.4%, these diagnoses were confirmed with pathogenic variants revealed; seven out of them were novel, including one CNV. All these genetic screening strategies revealed causative variants in 16.2% of the cases. Based on causative variants in the molecular diagnosis and genealogy analyses, a probable genetic etiology was found in ~ 50% of the cases. The present study highlights the relevance of GJB2/GJB6 as a cause of hearing loss in all Brazilian regions and the importance of screening unselected samples for estimating frequencies. Moreover, when a comprehensive screening is not available, molecular diagnosis can be enhanced by selecting probands for specific screenings.

show abstract

Section: Brazil's Regional Differences In Gjb2/gjb6 Contribution: Corroborating and Expanding Previous Studiessupporting

confidence: 90%

Molecular and genetic characterization of a large Brazilian cohort presenting hearing loss

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The p.V27I was found in one of our patients. The splice site mutation c.‐23+1G>A is positioned in the intron donor splice site and is anticipated to disrupt the splicing pattern, which results in no detectable mRNA (Castro et al, ). In a study on Iranian Azeri‐Turkish patients (Abe, Usami, Shinkawa, Kelley, & Kimberling, ), 16 (1 homozygous and 15 heterozygous) families out of the 174 families had c.‐23+1G>A mutation, with all of the 16 families demonstrating consanguineous marriage.…”

Section: Discussionmentioning

confidence: 99%

Frequency of GJB2 mutations, GJB6‐D13S1830 and GJB6‐D13S1854 deletions among patients with non‐syndromic hearing loss from the central region of Iran

Naddafnia

Noormohammadi

Irani

et al. 2019

Molec Gen & Gen Med

View full text Add to dashboard Cite

Background In the present study, we investigate the prevalence of the GJB 2 gene mutations, and deletions in the GJB 6 gene, namely del ( GJB 6‐D13S1830) and del ( GJB 6‐D13S1854), in patients with autosomal recessive non‐syndromic hearing loss (ARNSHL) from the central region of Iran. Methods One hundred and thirty‐one unrelated ARNSHL cases from the central part of Iran were recruited. Among them, 81% (106 cases) had at least two affected relatives. Coding and noncoding regions of the GJB 2 gene were sequenced. Multiplex PCR was used for analysis of del ( GJB 6‐D13S1830) and del ( GJB 6‐D13S1854) deletions in GJB 6. Results The GJB 2 variants were found in 16.79% (22/131) of the patients. The pathogenic variants were 21/131 (16.03%). The nonpathogenic variants were 1/131 (0. 07%). Allele frequency of the c.35delG as the pathogenic variant was the most common with 59.52% (25/42). The remaining pathogenic variants were c.235delC, p.T8M, p.R32H, p.R143Q, p.R143W, c‐23+1G>A. The only nonpathogenic variant was polymorphism p.V27I. Further segregation analysis showed that variant of p.R143Q might have incomplete penetrance. None of the patients had targeted deletions in the GJB 6 gene. Conclusion In comparison with reports from other areas of Iran, c.35delG demonstrates the highest frequency within the central region (accounting for 57.14% of cases), probably resulting from the founder effect and consanguineous marriage. The pathology of ARNSHL in such patients could be attributed to defects in Connexin 26 encoded by GJB 2.

show abstract

“…Evidence of the genetic etiology of HL in Brazil has been demonstrated by a number of independent studies (Pfeilsticker et al., ; Piatto et al., ; Bernardes et al., ; de Oliveira et al., ; Christiani et al., ; Batissoco et al., ; Cordeiro‐Silva et al., ; Motta et al., ; Castro et al., ; Manzoli et al., ; Ramos et al., ; Melo et al., ; Moreira et al., ). Most studies present data representative of Brazil's southeast region, while few studies show genetic HL data from the north and northeast regions.…”

Section: Introductionmentioning

confidence: 97%

Targeted Resequencing of Deafness Genes Reveals a FounderMYO15AVariant in Northeastern Brazil

Manzoli

Bademci

Acosta

et al. 2016

Annals of Human Genetics

View full text Add to dashboard Cite

Identifying the genetic etiology in a person with hearing loss (HL) is challenging due to the extreme genetic heterogeneity in HL and the population specific variability. In this study, after excluding GJB2 variants, targeted resequencing of 180 deafness-related genes revealed the causative variants in 11 of 19 (58%) Brazilian probands with autosomal recessive HL. Identified pathogenic variants were in MYO15A (10 families) and CLDN14 (1 family). Remarkably, the MYO15A p.(Val1400Met) variant was identified in 8 families from the city of Monte Santo in the Northeast region of Brazil. Haplotype analysis of this variant was consistent with a single founder. No other cases with this variant were detected among 105 simplex cases from other cities of Northeastern Brazil, suggesting that this variant is confined to a geographical region. This study suggests that it is feasible to develop population-specific screening for deafness variants once causative variants are identified in different geographical groups.

show abstract

A study of GJB2 and delGJB6-D13S1830 mutations in Brazilian non-syndromic deaf children from the Amazon region

Abstract: Mutant alleles on gene GJB2 were observed in 40% (31/77) of the subjects in the sample. Pathogenic variants were detected in only 12% (9/77) of the individuals. More studies are required to elucidate the genetic causes of hearing loss in miscegenated populations.

Cited by 14 publications

References 45 publications

Molecular and genetic characterization of a large Brazilian cohort presenting hearing loss

Molecular and genetic characterization of a large Brazilian cohort presenting hearing loss

Frequency of GJB2 mutations, GJB6‐D13S1830 and GJB6‐D13S1854 deletions among patients with non‐syndromic hearing loss from the central region of Iran

Targeted Resequencing of Deafness Genes Reveals a FounderMYO15AVariant in Northeastern Brazil

Contact Info

Product

Resources

About