Analysis of SLC26A4,FOXI1, and KCNJ10 Gene Variants in Patients with Incomplete Partition of the Cochlea and Enlarged Vestibular Aqueduct (EVA) Anomalies
Pathogenic variants in the SLC26A4, FOXI1, and KCNJ10 genes are associated with hearing loss (HL) and specific inner ear abnormalities (DFNB4). In the present study, phenotype analyses, including clinical data collection, computed tomography (CT), and audiometric examination, were performed on deaf...
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ftmdpi:oai:mdpi.com:/1422-0067/23/23/15372/ 2023-08-20T04:09:29+02:00 Analysis of SLC26A4,FOXI1, and KCNJ10 Gene Variants in Patients with Incomplete Partition of the Cochlea and Enlarged Vestibular Aqueduct (EVA) Anomalies Leonid A. Klarov Vera G. Pshennikova Georgii P. Romanov Aleksandra M. Cherdonova Aisen V. Solovyev Fedor M. Teryutin Nikolay V. Luginov Petr M. Kotlyarov Nikolay A. Barashkov agris 2022-12-06 application/pdf https://doi.org/10.3390/ijms232315372 EN eng Multidisciplinary Digital Publishing Institute Molecular Genetics and Genomics https://dx.doi.org/10.3390/ijms232315372 https://creativecommons.org/licenses/by/4.0/ International Journal of Molecular Sciences; Volume 23; Issue 23; Pages: 15372 SLC26A4 FOXI1 KCNJ10 genes hearing loss audiometric examination computer tomography inner ear anomalies incomplete partition type 1 (IP-1) incomplete partition type 2 (IP-2) enlarged vestibular aqueduct (EVA) genotype-phenotype analysis DFNB4 Pendred syndrome Eastern Siberia Russia Text 2022 ftmdpi https://doi.org/10.3390/ijms232315372 2023-08-01T07:40:06Z Pathogenic variants in the SLC26A4, FOXI1, and KCNJ10 genes are associated with hearing loss (HL) and specific inner ear abnormalities (DFNB4). In the present study, phenotype analyses, including clinical data collection, computed tomography (CT), and audiometric examination, were performed on deaf individuals from the Sakha Republic of Russia (Eastern Siberia). In cases with cochleovestibular malformations, molecular genetic analysis of the coding regions of the SLC26A4, FOXI1, and KCNJ10 genes associated with DFNB4 was completed. In six of the 165 patients (3.6%), CT scans revealed an incomplete partition of the cochlea (IP-1 and IP-2), in isolation or combined with an enlarged vestibular aqueduct (EVA) anomaly. Sequencing of the SLC26A4, FOXI1, and KCNJ10 genes was performed in these six patients. In the SLC26A4 gene, we identified four variants, namely c.85G>C p.(Glu29Gln), c.757A>G p.(Ile253Val), c.2027T>A p.(Leu676Gln), and c.2089+1G>A (IVS18+1G>A), which are known as pathogenic, as well as c.441G>A p.(Met147Ile), reported previously as a variant with uncertain significance. Using the AlphaFold algorithm, we found in silico evidence of the pathogenicity of this variant. We did not find any causative variants in the FOXI1 and KCNJ10 genes, nor did we find any evidence of digenic inheritance associated with double heterozygosity for these genes with monoallelic SLC26A4 variants. The contribution of biallelic SLC26A4 variants in patients with IP-1, IP-2, IP-2+EVA, and isolated EVA was 66.7% (DFNB4 in three patients, Pendred syndrome in one patient). Seventy-five percent of SLC26A4-biallelic patients had severe or profound HL. The morphology of the inner ear anomalies demonstrated that, among SLC26A4-biallelic patients, all types of incomplete partition of the cochlea are possible, from IP-1 and IP-2, to a normal cochlea. However, the dominant type of anomaly was IP-2+EVA (50.0%). This finding is very important for cochlear implantation, since the IP-2 anomaly does not have an increased risk ... Text Sakha Sakha Republic Siberia MDPI Open Access Publishing Sakha International Journal of Molecular Sciences 23 23 15372 |
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MDPI Open Access Publishing |
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ftmdpi |
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English |
topic |
SLC26A4 FOXI1 KCNJ10 genes hearing loss audiometric examination computer tomography inner ear anomalies incomplete partition type 1 (IP-1) incomplete partition type 2 (IP-2) enlarged vestibular aqueduct (EVA) genotype-phenotype analysis DFNB4 Pendred syndrome Eastern Siberia Russia |
spellingShingle |
SLC26A4 FOXI1 KCNJ10 genes hearing loss audiometric examination computer tomography inner ear anomalies incomplete partition type 1 (IP-1) incomplete partition type 2 (IP-2) enlarged vestibular aqueduct (EVA) genotype-phenotype analysis DFNB4 Pendred syndrome Eastern Siberia Russia Leonid A. Klarov Vera G. Pshennikova Georgii P. Romanov Aleksandra M. Cherdonova Aisen V. Solovyev Fedor M. Teryutin Nikolay V. Luginov Petr M. Kotlyarov Nikolay A. Barashkov Analysis of SLC26A4,FOXI1, and KCNJ10 Gene Variants in Patients with Incomplete Partition of the Cochlea and Enlarged Vestibular Aqueduct (EVA) Anomalies |
topic_facet |
SLC26A4 FOXI1 KCNJ10 genes hearing loss audiometric examination computer tomography inner ear anomalies incomplete partition type 1 (IP-1) incomplete partition type 2 (IP-2) enlarged vestibular aqueduct (EVA) genotype-phenotype analysis DFNB4 Pendred syndrome Eastern Siberia Russia |
description |
Pathogenic variants in the SLC26A4, FOXI1, and KCNJ10 genes are associated with hearing loss (HL) and specific inner ear abnormalities (DFNB4). In the present study, phenotype analyses, including clinical data collection, computed tomography (CT), and audiometric examination, were performed on deaf individuals from the Sakha Republic of Russia (Eastern Siberia). In cases with cochleovestibular malformations, molecular genetic analysis of the coding regions of the SLC26A4, FOXI1, and KCNJ10 genes associated with DFNB4 was completed. In six of the 165 patients (3.6%), CT scans revealed an incomplete partition of the cochlea (IP-1 and IP-2), in isolation or combined with an enlarged vestibular aqueduct (EVA) anomaly. Sequencing of the SLC26A4, FOXI1, and KCNJ10 genes was performed in these six patients. In the SLC26A4 gene, we identified four variants, namely c.85G>C p.(Glu29Gln), c.757A>G p.(Ile253Val), c.2027T>A p.(Leu676Gln), and c.2089+1G>A (IVS18+1G>A), which are known as pathogenic, as well as c.441G>A p.(Met147Ile), reported previously as a variant with uncertain significance. Using the AlphaFold algorithm, we found in silico evidence of the pathogenicity of this variant. We did not find any causative variants in the FOXI1 and KCNJ10 genes, nor did we find any evidence of digenic inheritance associated with double heterozygosity for these genes with monoallelic SLC26A4 variants. The contribution of biallelic SLC26A4 variants in patients with IP-1, IP-2, IP-2+EVA, and isolated EVA was 66.7% (DFNB4 in three patients, Pendred syndrome in one patient). Seventy-five percent of SLC26A4-biallelic patients had severe or profound HL. The morphology of the inner ear anomalies demonstrated that, among SLC26A4-biallelic patients, all types of incomplete partition of the cochlea are possible, from IP-1 and IP-2, to a normal cochlea. However, the dominant type of anomaly was IP-2+EVA (50.0%). This finding is very important for cochlear implantation, since the IP-2 anomaly does not have an increased risk ... |
format |
Text |
author |
Leonid A. Klarov Vera G. Pshennikova Georgii P. Romanov Aleksandra M. Cherdonova Aisen V. Solovyev Fedor M. Teryutin Nikolay V. Luginov Petr M. Kotlyarov Nikolay A. Barashkov |
author_facet |
Leonid A. Klarov Vera G. Pshennikova Georgii P. Romanov Aleksandra M. Cherdonova Aisen V. Solovyev Fedor M. Teryutin Nikolay V. Luginov Petr M. Kotlyarov Nikolay A. Barashkov |
author_sort |
Leonid A. Klarov |
title |
Analysis of SLC26A4,FOXI1, and KCNJ10 Gene Variants in Patients with Incomplete Partition of the Cochlea and Enlarged Vestibular Aqueduct (EVA) Anomalies |
title_short |
Analysis of SLC26A4,FOXI1, and KCNJ10 Gene Variants in Patients with Incomplete Partition of the Cochlea and Enlarged Vestibular Aqueduct (EVA) Anomalies |
title_full |
Analysis of SLC26A4,FOXI1, and KCNJ10 Gene Variants in Patients with Incomplete Partition of the Cochlea and Enlarged Vestibular Aqueduct (EVA) Anomalies |
title_fullStr |
Analysis of SLC26A4,FOXI1, and KCNJ10 Gene Variants in Patients with Incomplete Partition of the Cochlea and Enlarged Vestibular Aqueduct (EVA) Anomalies |
title_full_unstemmed |
Analysis of SLC26A4,FOXI1, and KCNJ10 Gene Variants in Patients with Incomplete Partition of the Cochlea and Enlarged Vestibular Aqueduct (EVA) Anomalies |
title_sort |
analysis of slc26a4,foxi1, and kcnj10 gene variants in patients with incomplete partition of the cochlea and enlarged vestibular aqueduct (eva) anomalies |
publisher |
Multidisciplinary Digital Publishing Institute |
publishDate |
2022 |
url |
https://doi.org/10.3390/ijms232315372 |
op_coverage |
agris |
geographic |
Sakha |
geographic_facet |
Sakha |
genre |
Sakha Sakha Republic Siberia |
genre_facet |
Sakha Sakha Republic Siberia |
op_source |
International Journal of Molecular Sciences; Volume 23; Issue 23; Pages: 15372 |
op_relation |
Molecular Genetics and Genomics https://dx.doi.org/10.3390/ijms232315372 |
op_rights |
https://creativecommons.org/licenses/by/4.0/ |
op_doi |
https://doi.org/10.3390/ijms232315372 |
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International Journal of Molecular Sciences |
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15372 |
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