Результаты исследований: Научные публикации в периодических изданиях › обзорная статья › Рецензирование
Functional Consequences of Pathogenic Variants of the GJB2 Gene (Cx26) Localized in Different Cx26 Domains. / Posukh, Olga L; Maslova, Ekaterina A; Danilchenko, Valeriia Yu и др.
в: Biomolecules, Том 13, № 10, 1521, 13.10.2023.Результаты исследований: Научные публикации в периодических изданиях › обзорная статья › Рецензирование
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TY - JOUR
T1 - Functional Consequences of Pathogenic Variants of the GJB2 Gene (Cx26) Localized in Different Cx26 Domains
AU - Posukh, Olga L
AU - Maslova, Ekaterina A
AU - Danilchenko, Valeriia Yu
AU - Zytsar, Marina V
AU - Orishchenko, Konstantin E
N1 - This work was supported by the Ministry of Education and Science of the Russian Federation (Grant No. FSUS-2020-0040 to O.L.P., E.A.M., V.Y.D. and K.E.O.) and by the projects of the Institute of Cytology and Genetics SB RAS (Grant No. FWNR-2022-0003 to V.Y.D. and M.V.Z., and Grant No. FWNR-2022-0021 to O.L.P.).
PY - 2023/10/13
Y1 - 2023/10/13
N2 - One of the most common forms of genetic deafness has been predominantly associated with pathogenic variants in the GJB2 gene, encoding transmembrane protein connexin 26 (Cx26). The Cx26 molecule consists of an N-terminal domain (NT), four transmembrane domains (TM1-TM4), two extracellular loops (EL1 and EL2), a cytoplasmic loop, and a C-terminus (CT). Pathogenic variants in the GJB2 gene, resulting in amino acid substitutions scattered across the Cx26 domains, lead to a variety of clinical outcomes, including the most common non-syndromic autosomal recessive deafness (DFNB1A), autosomal dominant deafness (DFNA3A), as well as syndromic forms combining hearing loss and skin disorders. However, for rare and poorly documented variants, information on the mode of inheritance is often lacking. Numerous in vitro studies have been conducted to elucidate the functional consequences of pathogenic GJB2 variants leading to amino acid substitutions in different domains of Cx26 protein. In this work, we summarized all available data on a mode of inheritance of pathogenic GJB2 variants leading to amino acid substitutions and reviewed published information on their functional effects, with an emphasis on their localization in certain Cx26 domains.
AB - One of the most common forms of genetic deafness has been predominantly associated with pathogenic variants in the GJB2 gene, encoding transmembrane protein connexin 26 (Cx26). The Cx26 molecule consists of an N-terminal domain (NT), four transmembrane domains (TM1-TM4), two extracellular loops (EL1 and EL2), a cytoplasmic loop, and a C-terminus (CT). Pathogenic variants in the GJB2 gene, resulting in amino acid substitutions scattered across the Cx26 domains, lead to a variety of clinical outcomes, including the most common non-syndromic autosomal recessive deafness (DFNB1A), autosomal dominant deafness (DFNA3A), as well as syndromic forms combining hearing loss and skin disorders. However, for rare and poorly documented variants, information on the mode of inheritance is often lacking. Numerous in vitro studies have been conducted to elucidate the functional consequences of pathogenic GJB2 variants leading to amino acid substitutions in different domains of Cx26 protein. In this work, we summarized all available data on a mode of inheritance of pathogenic GJB2 variants leading to amino acid substitutions and reviewed published information on their functional effects, with an emphasis on their localization in certain Cx26 domains.
KW - Humans
KW - Connexin 26/genetics
KW - Connexins/genetics
KW - Deafness/genetics
KW - Hearing Loss/genetics
KW - Hearing Loss, Sensorineural/genetics
KW - Mutation
KW - GJB2
KW - hereditary hearing loss
KW - non-synonymous variants
KW - Cx26 domains
UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85175014444&origin=inward&txGid=393c2268d4422b34d1c908ab94c7d500
UR - https://www.mendeley.com/catalogue/3f5158ce-28e5-36f1-be16-782749330459/
U2 - 10.3390/biom13101521
DO - 10.3390/biom13101521
M3 - Review article
C2 - 37892203
VL - 13
JO - Biomolecules
JF - Biomolecules
SN - 2218-273X
IS - 10
M1 - 1521
ER -
ID: 57516377