TY - JOUR

T1 - Selection of Diagnostically Significant Regions of the SLC26A4 Gene Involved in Hearing Loss

AU - Danilchenko, Valeriia Yu

AU - Zytsar, Marina V.

AU - Maslova, Ekaterina A.

AU - Posukh, Olga L.

N1 - Funding Information: This work was supported by the Russian Science Foundation grant No 21-75-00030, https://rscf.ru/en/project/21-75-00030/ (to M.V.Z., E.A.M. and V.Y.D.) and by the Ministry of Education and Science of Russian Federation (grant No FSUS-2020-0040) (to O.L.P.). Publisher Copyright: © 2022 by the authors.

PY - 2022/11

Y1 - 2022/11

N2 - Screening pathogenic variants in the SLC26A4 gene is an important part of molecular genetic testing for hearing loss (HL) since they are one of the common causes of hereditary HL in many populations. However, a large size of the SLC26A4 gene (20 coding exons) predetermines the difficulties of its complete mutational analysis, especially in large samples of patients. In addition, the regional or ethno-specific prevalence of SLC26A4 pathogenic variants has not yet been fully elucidated, except variants c.919-2A>G and c.2168A>G (p.His723Arg), which have been proven to be most common in Asian populations. We explored the distribution of currently known pathogenic and likely pathogenic (PLP) variants across the SLC26A4 gene sequence presented in the Deafness Variation Database for the selection of potential diagnostically important parts of this gene. As a result of this bioinformatic analysis, we found that molecular testing ten SLC26A4 exons (4, 6, 10, 11, 13–17 and 19) with flanking intronic regions can provide a diagnostic rate of 61.9% for all PLP variants in the SLC26A4 gene. The primary sequencing of these SLC26A4 regions may be applied as an initial effective diagnostic testing in samples of patients of unknown ethnicity or as a subsequent step after the targeted testing of already-known ethno- or region-specific pathogenic SLC26A4 variants.

AB - Screening pathogenic variants in the SLC26A4 gene is an important part of molecular genetic testing for hearing loss (HL) since they are one of the common causes of hereditary HL in many populations. However, a large size of the SLC26A4 gene (20 coding exons) predetermines the difficulties of its complete mutational analysis, especially in large samples of patients. In addition, the regional or ethno-specific prevalence of SLC26A4 pathogenic variants has not yet been fully elucidated, except variants c.919-2A>G and c.2168A>G (p.His723Arg), which have been proven to be most common in Asian populations. We explored the distribution of currently known pathogenic and likely pathogenic (PLP) variants across the SLC26A4 gene sequence presented in the Deafness Variation Database for the selection of potential diagnostically important parts of this gene. As a result of this bioinformatic analysis, we found that molecular testing ten SLC26A4 exons (4, 6, 10, 11, 13–17 and 19) with flanking intronic regions can provide a diagnostic rate of 61.9% for all PLP variants in the SLC26A4 gene. The primary sequencing of these SLC26A4 regions may be applied as an initial effective diagnostic testing in samples of patients of unknown ethnicity or as a subsequent step after the targeted testing of already-known ethno- or region-specific pathogenic SLC26A4 variants.

KW - bioinformatic analysis

KW - hearing loss

KW - molecular testing

KW - pathogenic variants

KW - pendrin

KW - SLC26A4

KW - Humans

KW - Mutation

KW - Hearing Loss/diagnosis

KW - Sulfate Transporters/genetics

KW - Hearing Loss, Sensorineural/genetics

KW - Deafness/genetics

UR - http://www.scopus.com/inward/record.url?scp=85141619084&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/7ddf0aae-fcb1-3350-9eb3-fc8eb065f77a/

U2 - 10.3390/ijms232113453

DO - 10.3390/ijms232113453

M3 - Article

C2 - 36362242

AN - SCOPUS:85141619084

VL - 23

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 21

M1 - 13453

ER -