Distribution and phenotype of<i>GJB2</i>mutations in 102 Sicilian patients with congenital non syndromic sensorineural hearing loss

Salvago, Pietro; Martines, Enrico; Mattina, Eleonora La; Mucia, Marianna; Sammarco, P.; Sireci, Federico; Martines, Francesco

doi:10.3109/14992027.2014.905717

Cited by 5 publications

(3 citation statements)

References 42 publications

(37 reference statements)

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“…In our study, the c.35delG allele accounted for 65.5% of mutated chromosomes, which is in accordance with data previously reported for Southern Europe and the Mediterranean area (Antoniadi et al., ; Gasparini et al., ), but it is in contrast with a higher c.35delG prevalence of 90.36% and 76.3% found in Western Sicily (Martines et al., ; Salvago et al., ). There are several possible explanations for the different distribution of c.35delG allele between the Sicilian geographic areas.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of Deafness‐Associated Connexin‐26 (GJB2) and Connexin‐30 (GJB6) Pathogenic Alleles in a Large Patient Cohort from Eastern Sicily

Amorini

Romeo

Bruno

et al. 2015

Annals of Human Genetics

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SummaryMutations in the gene encoding the gap junction protein connexin 26 (GJB2) and connexin 30 (GJB6) have been shown to be a major contributor to prelingual, sensorineural, nonsyndromic deafness.The aim of this study was to characterize and establish the prevalence of GJB2 and GJB6 gene alterations in 196 patients affected by sensorineural, nonsyndromic hearing loss, from Eastern Sicily. We performed sequence analysis of GJB2 and identified sequence variants in 68 out of 196 patients (34.7%); (28 homozygous for c.35delG, 22 compound heterozygous and 11 with only one variant allele).

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Section: Discussionmentioning

confidence: 99%

Prevalence of Deafness‐Associated Connexin‐26 (GJB2) and Connexin‐30 (GJB6) Pathogenic Alleles in a Large Patient Cohort from Eastern Sicily

Amorini

Romeo

Bruno

et al. 2015

Annals of Human Genetics

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“…NSHL accounts for the vast majority of hereditary HL cases and includes, according to the pattern of inheritance, autosomal recessive cases (~80%, labeled as “DFNB”), autosomal dominant (~20%, labeled as “DFNA”) X-linked or mitochondrial cases (<1%) (Stelma and Bhutta, 2014). In Italy, from 20 to 40% of cases are caused by mutations in GJB2 gene (Cama et al, 2009; Primignani et al, 2009; Salvago et al, 2014), making it the major player. However, as expected, considering the unique and complex structure of the inner ear, many other genes have been found to be involved in the hearing phenotype.…”

Section: Introductionmentioning

confidence: 99%

Genomic Studies in a Large Cohort of Hearing Impaired Italian Patients Revealed Several New Alleles, a Rare Case of Uniparental Disomy (UPD) and the Importance to Search for Copy Number Variations

et al. 2018

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Hereditary hearing loss (HHL) is a common disorder characterized by a huge genetic heterogeneity. The definition of a correct molecular diagnosis is essential for proper genetic counseling, recurrence risk estimation, and therapeutic options. From 20 to 40% of patients carry mutations in GJB2 gene, thus, in more than half of cases it is necessary to look for causative variants in the other genes so far identified (~100). In this light, the use of next-generation sequencing technologies has proved to be the best solution for mutational screening, even though it is not always conclusive. Here we describe a combined approach, based on targeted re-sequencing (TRS) of 96 HHL genes followed by high-density SNP arrays, aimed at the identification of the molecular causes of non-syndromic HHL (NSHL). This strategy has been applied to study 103 Italian unrelated cases, negative for mutations in GJB2, and led to the characterization of 31% of them (i.e., 37% of familial and 26.3% of sporadic cases). In particular, TRS revealed TECTA and ACTG1 genes as major players in the Italian population. Furthermore, two de novo missense variants in ACTG1 have been identified and investigated through protein modeling and molecular dynamics simulations, confirming their likely pathogenic effect. Among the selected patients analyzed by SNP arrays (negative to TRS, or with a single variant in a recessive gene) a molecular diagnosis was reached in ~36% of cases, highlighting the importance to look for large insertions/deletions. Moreover, copy number variants analysis led to the identification of the first case of uniparental disomy involving LOXHD1 gene. Overall, taking into account the contribution of GJB2, plus the results from TRS and SNP arrays, it was possible to reach a molecular diagnosis in ~51% of NSHL cases. These data proved the usefulness of a combined approach for the analysis of NSHL and for the definition of the epidemiological picture of HHL in the Italian population.

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“…Genetic factors are important for the pathogenesis of hearing impairment. Approximately 60% of congenital hearing impairment in developed countries has genetic causes; this proportion has been increasing due to the improvement of public health conditions and consequent reduction of hearing impairment linked to other causes [ 6 ]. Thus it is of great importance to study the genetic factors in congenital NSHI.…”

Section: Introductionmentioning

confidence: 99%

Associations Between TGFA/TGFB3/MSX1 Gene Polymorphisms and Congenital Non-Syndromic Hearing Impairment in a Chinese Population

Deng

2016

Med Sci Monit

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BackgroundThe aim of this study was to investigate whether the TGFA/TGFB3/MSX1 gene polymorphisms and haplotypes lead to individual differences between congenital non-syndromic hearing impairment (NSHI) patients and normal people in a Chinese population and to analyze the risk factors for NSHI.Material/MethodsBetween December 2010 and September 2014, 343 congenital NSHI patients were recruited as cases, and 272 healthy subjects were recruited as controls. Denaturing high-performance liquid chromatography (DHPLC) was used to identify genotypes, SHEsis software was used to conduct gene linkage disequilibrium and haplotype analyses, and regression analysis was performed to identify risk factors for congenital NSHI.ResultsThe distribution of genotype frequencies and allele frequencies of TGFA rs3771494, TGFB3 rs3917201 and rs2268626, and MSX1 rs3821949 and rs62636562 were significantly different between the case and the control groups (all P<0.05). TGFA/TGFB3/MSX1 gene rs3771494, rs1058213, rs3917201, rs2268626, rs3821949, and rs62636562 haplotype analysis showed that haplotype CCGTAC and TTACGT might be protective factors (both P<0.001), while TTGCGC might be a risk factor for the normal population (P<0.001). The other risk factors include paternal smoking, advanced maternal age, maternal sickness history, maternal contact with pesticides or similar drugs, maternal abortion history, maternal medication history, maternal passive smoking history during pregnancy, rs3771494 CT, rs2268626 CC and TC, and rs3821949 GG and AG genotypes were risk factors (all P<0.05), while maternal vitamin supplements during pregnancy, rs3917201 GA, rs62636562 TT and CT genotypes were protective factors for congenital NSHI (all P<0.05).Conclusionsrs3771494, rs3917201, rs2268626, rs3821949 and rs62636562 might be associated with congenital NSHI.

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Distribution and phenotype ofGJB2mutations in 102 Sicilian patients with congenital non syndromic sensorineural hearing loss

Cited by 5 publications

References 42 publications

Prevalence of Deafness‐Associated Connexin‐26 (GJB2) and Connexin‐30 (GJB6) Pathogenic Alleles in a Large Patient Cohort from Eastern Sicily

Prevalence of Deafness‐Associated Connexin‐26 (GJB2) and Connexin‐30 (GJB6) Pathogenic Alleles in a Large Patient Cohort from Eastern Sicily

Genomic Studies in a Large Cohort of Hearing Impaired Italian Patients Revealed Several New Alleles, a Rare Case of Uniparental Disomy (UPD) and the Importance to Search for Copy Number Variations

Associations Between TGFA/TGFB3/MSX1 Gene Polymorphisms and Congenital Non-Syndromic Hearing Impairment in a Chinese Population

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