Results of molecular genetic testing in Russian patients with Pendred syndrome and allelic disorders

Миронович, О. Л.; Bliznetz, E. A.; Маркова, Т Г; Geptner, E. N.; Lalayants, M. R.; Зеликович, Е И; Таварткиладзе, Г. А.; Polyakov, A. V.

doi:10.1134/s1022795416120085

Cited by 2 publications

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“…In Russia, the FOXI1 and KCNJ10 genes have not previously been analyzed among patients with HL. However, pathogenic variant analysis of the SLC26A4 gene was previously performed in 246 families with HL cases from the Bashkortostan Republic of Russia (Volga–Ural Region) [ 50 ] and in 20 patients with Pendred syndrome, EVA, and/or Mondini anomalies in a geographically dispersed sample [ 51 ]. Analyses of pathogenic variants of the SLC26A4 gene in 313 patients with HL in the Tyva and Altai Republics of Russia (Southern Siberia) revealed the different contributions of biallelic SLC26A4 pathogenic variants to the etiology of HL (28.2% in Tuvinian and 4.3% in Altaian patients) [ 52 ].…”

Section: Introductionmentioning

confidence: 99%

“…Analyses of pathogenic variants of the SLC26A4 gene in 313 patients with HL in the Tyva and Altai Republics of Russia (Southern Siberia) revealed the different contributions of biallelic SLC26A4 pathogenic variants to the etiology of HL (28.2% in Tuvinian and 4.3% in Altaian patients) [ 52 ]. In total, 14 recessive pathogenic variants of the SLC26A4 gene were identified: c.85G>C p.(Glu29Gln), c.l49T>G p.(Leu50Arg), c.170C>A p.(Ser57Ter), c.222G>T p.(Trp74Cys), c.317C>A p.(Ala106Asp), c.919-2A>G (IVS7-2A>G), c.1001G>T p.(Glu334Val), c.1003T>C p.(Phe335Leu), c.1229C>T p.(Thr410Met), c.1790T>C p.(Leu597Ser), c.1545T>G p.(Phe515Leu), c.2027T>A p.(Leu676Gln), c.2034+1G>A (a splice site variant), and c.2168A>G p.(His723Arg) [ 50 , 51 , 52 ].…”

Section: Introductionmentioning

confidence: 99%

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Analysis of SLC26A4, FOXI1, and KCNJ10 Gene Variants in Patients with Incomplete Partition of the Cochlea and Enlarged Vestibular Aqueduct (EVA) Anomalies

Klarov

Pshennikova

Romanov

et al. 2022

IJMS

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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 of “gushers” and recurrent meningitis.

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Section: Introductionmentioning

confidence: 99%