scholarly journals Evidence for Central Asian Origin of the p.Val27Ile Variant in the GJB2 Gene

2014 ◽  
Vol 2014 ◽  
pp. 1-8
Author(s):  
Guille García Sánchez ◽  
Alfonso Alfaro-Rodríguez ◽  
Adrián Poblano
Keyword(s):  
Hearing Impairment ◽  
Mexico City ◽  
Common Ancestor ◽  
Gjb2 Gene ◽  
Wild Type ◽  
Altai Republic ◽  
Asian Origin ◽  
Mexican Mestizo ◽  
Central Asian ◽  
Syndromic Hearing Impairment

The mutations in the GJB2 gene are the most common cause of nonsyndromic hearing impairment and they are associated with the population’s ethnic background. The p.Val27Ile is frequent in both Asia and America. In this retrospective study, we report the findings from the GJB2 screening and the audiological exams conducted on 125 Mexican mestizo patients with non-syndromic hearing impairment; they were treated at the Instituto Nacional de Rehabilitacion in Mexico City. The most frequent audiometric findings were bilateral, symmetrical, and profound hearing impairment. The allele frequencies in the GJB2 screening were p.Val27Ile 15%, other mutations 5%, and wild type 80%. We found no correlation between GJB2 genotype and auditory phenotype. The high allele frequency of p.Val27Ile was a very interesting finding. Our research suggests that p.Val27Ile arose in an ancient common ancestor who lived in Altai Republic and then the polymorphism was brought to America by its first inhabitants, the Amerindians. These results enhance our understanding of the peopling of the America, which remains unresolved.

scholarly journals GJB4 and GJC3 variants in non-syndromic hearing impairment in Ghana

2020 ◽  
Vol 245 (15) ◽  
pp. 1355-1367 ◽  
Author(s):  
Samuel M Adadey ◽  
Kevin K Esoh ◽  
Osbourne Quaye ◽  
Geoffrey K Amedofu ◽  
Gordon A Awandare ◽  
...  
Keyword(s):  
Hearing Impairment ◽  
Hearing Impaired ◽  
The Body ◽  
Wild Type ◽  
Mutant Proteins ◽  
Coding Regions ◽  
Multiplex Families ◽  
Schools For The Deaf ◽  
Syndromic Hearing Impairment ◽  
Study Participants

The contribution of GJB4 and GJC3 gene variants to hearing impairment in Africa has not yet been studied. Here, we investigated the contribution of these genes to autosomal recessive non-syndromic hearing impairment in Ghanaian children. Hearing-impaired children from 141 simplex and 59 multiplex families were enrolled from 11 schools for the deaf in Ghana. The coding regions of GJB4 and GJC3 were amplified, sequenced, and analyzed for the study participants previously found to be negative for GJB2 and GJB6 variants. Seven GJB4 and one GJC3 variants were identified. One out of the seven GJB4 variants was classified as likely pathogenic, while the others were either benign or synonymous. The likely pathogenic variant (p.Asn119Thr/rs190460237) was predicted to be likely associated with hearing impairment. We modeled the wild-type and mutant proteins of this variant (p.Asn119Thr) to evaluate the effect of the mutation on protein structure and ligand-binding properties. The mutant and not the wild type had the potential to bind N-Ethyl-5ʹ-Carboxamido Adenosine (DB03719) which was due to a slight structural change that was observed. No clinically relevant variant was identified in the GJC3 gene. We report for the first time a likely pathogenic GJB4 variant that may be associated with non-syndromic hearing impairment in Ghana; the finding will add to the body of evidence of the contribution of GJB4 to hearing impairment cases around the world. Impact statement Although connexins are known to be the major genetic factors associated with HI, only a few studies have investigated GJB4 and GJC3 variants among hearing-impaired patients. This study is the first to report GJB4 and GJC3 variants from an African HI cohort. We have demonstrated that GJB4 and GJC3 genes may not contribute significantly to HI in Ghana, hence these genes should not be considered for routine clinical screening in Ghana. However, it is important to study a larger population to determine the association of GJB4 and GJC3 variants with HI.

Screening of families with autosomal recessive non-syndromic hearing impairment (ARNSHI) for mutations in GJB2 gene: Indian scenario

2003 ◽  
Vol 120A (2) ◽  
pp. 180-184 ◽  
Author(s):  
Manjula Maheshwari ◽  
R. Vijaya ◽  
Manju Ghosh ◽  
Shivaram Shastri ◽  
Madhulika Kabra ◽  
...  
Keyword(s):  
Hearing Impairment ◽  
Autosomal Recessive ◽  
Gjb2 Gene ◽  
Syndromic Hearing Impairment ◽  
Indian Scenario

scholarly journals GJB2 and GJB6 Mutations in Hereditary Recessive Non-Syndromic Hearing Impairment in Cameroon

Genes ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 844 ◽  
Author(s):  
Edmond Tingang Wonkam ◽  
Emile Chimusa ◽  
Jean Jacques Noubiap ◽  
Samuel Mawuli Adadey ◽  
Jean Valentin F. Fokouo ◽  
...  
Keyword(s):  
Hearing Impairment ◽  
Sanger Sequencing ◽  
Usher Syndrome ◽  
Autosomal Recessive Inheritance ◽  
Pedigree Analysis ◽  
Gjb2 Gene ◽  
Coding Region ◽  
Environmental Causes ◽  
Syndromic Hearing Impairment

This study aimed to investigate GJB2 (connexin 26) and GJB6 (connexin 30) mutations associated with familial non-syndromic childhood hearing impairment (HI) in Cameroon. We selected only families segregating HI, with at least two affected individuals and with strong evidence of non-environmental causes. DNA was extracted from peripheral blood, and the entire coding region of GJB2 was interrogated using Sanger sequencing. Multiplex PCR and Sanger sequencing were used to analyze the prevalence of the GJB6-D3S1830 deletion. A total of 93 patients, belonging to 41 families, were included in the analysis. Hearing impairment was sensorineural in 51 out of 54 (94.4%) patients. Pedigree analysis suggested autosomal recessive inheritance in 85.4% (35/41) of families. Hearing impairment was inherited in an autosomal dominant and mitochondrial mode in 12.2% (5/41) and 2.4% (1/41) of families, respectively. Most HI participants were non-syndromic (92.5%; 86/93). Four patients from two families presented with type 2 Waardenburg syndrome, and three cases of type 2 Usher syndrome were identified in one family. No GJB2 mutations were found in any of the 29 families with non-syndromic HI. Additionally, the GJB6-D3S1830 deletion was not identified in any of the HI patients. This study confirms that mutations in the GJB2 gene and the del(GJB6-D13S1830) mutation do not contribute to familial HI in Cameroon.

GJB2 gene mutations in newborns with non-syndromic hearing impairment in Northern China

2004 ◽  
Vol 197 (1-2) ◽  
pp. 19-23 ◽  
Author(s):  
Gui-zhi Shi ◽  
Lu-xia Gong ◽  
Xiao-hu Xu ◽  
Wen-ying Nie ◽  
Qian Lin ◽  
...  
Keyword(s):  
Hearing Impairment ◽  
Gene Mutations ◽  
Northern China ◽  
Gjb2 Gene ◽  
Syndromic Hearing Impairment

scholarly journals Whole mitochondrial genome screening in maternally inherited non-syndromic hearing impairment using a microarray resequencing mitochondrial DNA chip

2007 ◽  
Vol 15 (11) ◽  
pp. 1145-1155 ◽  
Author(s):  
Marianne Lévêque ◽  
Sandrine Marlin ◽  
Laurence Jonard ◽  
Vincent Procaccio ◽  
Pascal Reynier ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Mitochondrial Genome ◽  
Hearing Impairment ◽  
Dna Chip ◽  
Genome Screening ◽  
Syndromic Hearing Impairment

scholarly journals Concurrent genetic and standard screening test for hearing reduction

2020 ◽  
Vol 66 (2) ◽  
pp. 35-40
Author(s):  
Marina Davcheva Chakar ◽  
Gjorgji Bozhinovski ◽  
Emilija Shukarova Stefanovska ◽  
Dejan Trajkov
Keyword(s):  
Hearing Loss ◽  
Hearing Impairment ◽  
Genetic Screening ◽  
Screening Test ◽  
Screening Program ◽  
Deaf Child ◽  
Hearing Screening ◽  
Pathogenic Variant ◽  
Gjb2 Gene ◽  
Brainstem Response

Reduction of hearing is the most common sensory impairment among newborns with an incidence of 1-3 per 1000 births. Introduction of an Auditory Newborn screening program allows early identification of hearing impairment. Mainly, congenital hearing loss in early childhood is a result of genetic changes. Due to high frequency of GJB2 pathogenic variants, its molecular characterization among sensorineural hearing reduction cases is already conducted as a routine analysis in many countries. The aim of this study is to show our initial results in the effort to determine whether genetic screening along with the standard hearing screening in newborns is justified. Otoacoustic emission (OAE) method was conducted in 223 newborns at risk of hearing impairment. Among them, 7 did not pass the test in both ears while 9 exhibited one-sided hearing loss. In all 7 children with indication of profound bilateral deafness, the diagnosis was confirmed using auditory brainstem response. Genetic screening of GJB2 gene was performed in 6 of them. Genetic analysis of GJB2 revealed homozygous state of the most common pathogenic variant 35delG in 3 (50%) of the analyzed infants. In the remaining 3 no pathogenic variant was determined. The results indicate that performing auditory OAE together with genetic screening is justified. In newborns who have not passed the hearing screening test and have profound hearing loss, without other syndrome traits, screening for mutations of GJB2 gene should be conducted. Genetic screening enables establishment of early definite diagnosis for deafness and helps in conducting adequate therapy providing timely rehabilitation and social inclusion of deaf child. Key words: hearing loss, genetic screening, auditory screening, GJB2 gene

scholarly journals Old gene, new phenotype: splice-altering variants in CEACAM16 cause recessive non-syndromic hearing impairment

2018 ◽  
Vol 55 (8) ◽  
pp. 555-560 ◽  
Author(s):  
Kevin T Booth ◽  
Kimia Kahrizi ◽  
Hossein Najmabadi ◽  
Hela Azaiez ◽  
Richard JH Smith
Keyword(s):  
Hearing Loss ◽  
Hearing Impairment ◽  
Loss Of Function ◽  
Bioinformatics Pipeline ◽  
Exon 2 ◽  
Reading Frame ◽  
Sequencing Platform ◽  
Syndromic Hearing Impairment ◽  
Generation Sequencing

BackgroundHearing loss is a genetically and phenotypically heterogeneous disorder.ObjectivesThe purpose of this study was to determine the genetic cause underlying the postlingual progressive hearing loss in two Iranian families.MethodsWe used OtoSCOPE, a next-generation sequencing platform targeting >150 genes causally linked to deafness, to screen two deaf probands. Data analysis was completed using a custom bioinformatics pipeline, and variants were functionally assessed using minigene splicing assays.ResultsWe identified two homozygous splice-altering variants (c.37G>T and c.662–1G>C) in the CEACAM16 gene, segregating with the deafness in each family. The minigene splicing results revealed the c.37G>T results in complete skipping of exon 2 and loss of the AUG start site. The c.662–1G>C activates a cryptic splice site inside exon 5 resulting in a shift in the mRNA reading frame.ConclusionsThese results suggest that loss-of-function mutations in CEACAM16 result in postlingual progressive hearing impairment and further support the role of CEACAM16 in auditory function.

scholarly journals Origins of the Recent Emergence of Plasmodium falciparum Pyrimethamine Resistance Alleles in Madagascar

2010 ◽  
Vol 54 (6) ◽  
pp. 2323-2329 ◽  
Author(s):  
Valérie Andriantsoanirina ◽  
Christiane Bouchier ◽  
Magali Tichit ◽  
Martial Jahevitra ◽  
Stéphane Rabearimanana ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Intermittent Preventive Treatment ◽  
Preventive Treatment ◽  
Single Mutation ◽  
Wild Type ◽  
Triple Mutant ◽  
Asian Origin ◽  
Recent Emergence ◽  
Malaria During Pregnancy ◽  
Mutation Allele

ABSTRACT The combination of sulfadoxine-pyrimethamine is recommended for use as intermittent preventive treatment of malaria during pregnancy and is deployed in Africa. The emergence and the spread of resistant parasites are major threats to such an intervention. We have characterized the Plasmodium falciparum dhfr (pfdhfr) haplotypes and flanking microsatellites in 322 P. falciparum isolates collected from the Comoros Islands and Madagascar. One hundred fifty-six (48.4%) carried the wild-type pfdhfr allele, 19 (5.9%) carried the S108N single-mutation allele, 30 (9.3%) carried the I164L single-mutation allele, 114 (35.4%) carried the N51I/C59R/S108N triple-mutation allele, and 3 (1.0%) carried the N51I/C59R/S108N/I164L quadruple-mutation allele. Microsatellite analysis showed the introduction from the Comoros Islands of the ancestral pfdhfr triple mutant allele of Asian origin and its spread in Madagascar. Evidence for the emergence on multiple occasions of the I164L single-mutation pfdhfr allele in Madagascar was also obtained. Thus, the conditions required to generate mutants with quadruple mutations are met in Madagascar, representing a serious threat to current drug policy.

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