Expanding the Molecular Landscape of Androgen Insensitivity Syndrome Through Next-Generation Sequencing

Tadeusz Kałużewski,1,2 Iwona Pinkier,1 Urszula Wysocka,1 Jordan Sałamunia,2 Łukasz Kępczyński,1,2 Małgorzata Piotrowicz,1 Bogdan Kałużewski,2 Agnieszka Gach1 1Department of Genetics, Polish Mother’s Memoria...

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Main Authors: Kałużewski T, Pinkier I, Wysocka U, Sałamunia J, Kępczyński Ł, Piotrowicz M, Kałużewski B, Gach A
Format: Article
Language:English
Published: Dove Medical Press 2024-12-01
Series:The Application of Clinical Genetics
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Online Access:https://www.dovepress.com/expanding-the-molecular-landscape-of-androgen-insensitivity-syndrome-t-peer-reviewed-fulltext-article-TACG
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author Kałużewski T
Pinkier I
Wysocka U
Sałamunia J
Kępczyński Ł
Piotrowicz M
Kałużewski B
Gach A
author_facet Kałużewski T
Pinkier I
Wysocka U
Sałamunia J
Kępczyński Ł
Piotrowicz M
Kałużewski B
Gach A
author_sort Kałużewski T
collection DOAJ
description Tadeusz Kałużewski,1,2 Iwona Pinkier,1 Urszula Wysocka,1 Jordan Sałamunia,2 Łukasz Kępczyński,1,2 Małgorzata Piotrowicz,1 Bogdan Kałużewski,2 Agnieszka Gach1 1Department of Genetics, Polish Mother’s Memorial Hospital Research Institute, Lodz, 93-338, Poland; 2R&D Division, Laboratory of Medical Genetics, GENOS Sp. z o.o., Lodz, 91-033, PolandCorrespondence: Tadeusz Kałużewski, Email tadeusz.kaluzewski@iczmp.edu.plAbstract: Androgen insensitivity syndrome (AIS) is an X-linked genetic disorder caused by mutations in the androgen receptor gene (AR), leading to impaired androgen signaling and resulting in varying degrees of undermasculinization in individuals with a 46,XY karyotype. This study aimed to expand the molecular landscape of AIS by identifying and characterizing pathogenic variants in the AR gene via next-generation sequencing (NGS). Molecular diagnostics revealed eight distinct variants within the AR gene, two of which had not been previously described. These include the following novel variants: c.3G>A, and c.1344_1345insTA. This study broadens the spectrum of known AR gene mutations associated with AIS and highlights the critical role of molecular diagnostics in the accurate classification of variants. These findings will aid in enhancing the clinical management and genetic counseling of individuals affected by AIS.Keywords: androgen insensitivity syndrome, AIS, androgen receptor gene, AR gene, next-generation sequencing, NGS, disorders of sex development, complete androgen insensitivity syndrome, CAIS
format Article
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publishDate 2024-12-01
publisher Dove Medical Press
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series The Application of Clinical Genetics
spelling doaj-art-7ae8be69f59b4d09aa8a467776a42a7e2025-08-20T01:59:43ZengDove Medical PressThe Application of Clinical Genetics1178-704X2024-12-01Volume 1720521498649Expanding the Molecular Landscape of Androgen Insensitivity Syndrome Through Next-Generation SequencingKałużewski TPinkier IWysocka USałamunia JKępczyński ŁPiotrowicz MKałużewski BGach ATadeusz Kałużewski,1,2 Iwona Pinkier,1 Urszula Wysocka,1 Jordan Sałamunia,2 Łukasz Kępczyński,1,2 Małgorzata Piotrowicz,1 Bogdan Kałużewski,2 Agnieszka Gach1 1Department of Genetics, Polish Mother’s Memorial Hospital Research Institute, Lodz, 93-338, Poland; 2R&D Division, Laboratory of Medical Genetics, GENOS Sp. z o.o., Lodz, 91-033, PolandCorrespondence: Tadeusz Kałużewski, Email tadeusz.kaluzewski@iczmp.edu.plAbstract: Androgen insensitivity syndrome (AIS) is an X-linked genetic disorder caused by mutations in the androgen receptor gene (AR), leading to impaired androgen signaling and resulting in varying degrees of undermasculinization in individuals with a 46,XY karyotype. This study aimed to expand the molecular landscape of AIS by identifying and characterizing pathogenic variants in the AR gene via next-generation sequencing (NGS). Molecular diagnostics revealed eight distinct variants within the AR gene, two of which had not been previously described. These include the following novel variants: c.3G>A, and c.1344_1345insTA. This study broadens the spectrum of known AR gene mutations associated with AIS and highlights the critical role of molecular diagnostics in the accurate classification of variants. These findings will aid in enhancing the clinical management and genetic counseling of individuals affected by AIS.Keywords: androgen insensitivity syndrome, AIS, androgen receptor gene, AR gene, next-generation sequencing, NGS, disorders of sex development, complete androgen insensitivity syndrome, CAIShttps://www.dovepress.com/expanding-the-molecular-landscape-of-androgen-insensitivity-syndrome-t-peer-reviewed-fulltext-article-TACGandrogen insensitivity syndromeaisandrogen receptor genear genenext-generation sequencingngsdisorders of sex developmentcomplete androgen insensitivity syndromecais.
spellingShingle Kałużewski T
Pinkier I
Wysocka U
Sałamunia J
Kępczyński Ł
Piotrowicz M
Kałużewski B
Gach A
Expanding the Molecular Landscape of Androgen Insensitivity Syndrome Through Next-Generation Sequencing
The Application of Clinical Genetics
androgen insensitivity syndrome
ais
androgen receptor gene
ar gene
next-generation sequencing
ngs
disorders of sex development
complete androgen insensitivity syndrome
cais.
title Expanding the Molecular Landscape of Androgen Insensitivity Syndrome Through Next-Generation Sequencing
title_full Expanding the Molecular Landscape of Androgen Insensitivity Syndrome Through Next-Generation Sequencing
title_fullStr Expanding the Molecular Landscape of Androgen Insensitivity Syndrome Through Next-Generation Sequencing
title_full_unstemmed Expanding the Molecular Landscape of Androgen Insensitivity Syndrome Through Next-Generation Sequencing
title_short Expanding the Molecular Landscape of Androgen Insensitivity Syndrome Through Next-Generation Sequencing
title_sort expanding the molecular landscape of androgen insensitivity syndrome through next generation sequencing
topic androgen insensitivity syndrome
ais
androgen receptor gene
ar gene
next-generation sequencing
ngs
disorders of sex development
complete androgen insensitivity syndrome
cais.
url https://www.dovepress.com/expanding-the-molecular-landscape-of-androgen-insensitivity-syndrome-t-peer-reviewed-fulltext-article-TACG
work_keys_str_mv AT kałuzewskit expandingthemolecularlandscapeofandrogeninsensitivitysyndromethroughnextgenerationsequencing
AT pinkieri expandingthemolecularlandscapeofandrogeninsensitivitysyndromethroughnextgenerationsequencing
AT wysockau expandingthemolecularlandscapeofandrogeninsensitivitysyndromethroughnextgenerationsequencing
AT sałamuniaj expandingthemolecularlandscapeofandrogeninsensitivitysyndromethroughnextgenerationsequencing
AT kepczynskił expandingthemolecularlandscapeofandrogeninsensitivitysyndromethroughnextgenerationsequencing
AT piotrowiczm expandingthemolecularlandscapeofandrogeninsensitivitysyndromethroughnextgenerationsequencing
AT kałuzewskib expandingthemolecularlandscapeofandrogeninsensitivitysyndromethroughnextgenerationsequencing
AT gacha expandingthemolecularlandscapeofandrogeninsensitivitysyndromethroughnextgenerationsequencing