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Novel Mutations Segregating with Complete Androgen Insensitivity Syndrome and Their Molecular Characteristics
We analyzed three cases of Complete Androgen Insensitivity Syndrome (CAIS) and report three hitherto undisclosed causes of the disease. RNA-Seq, Real-timePCR, Western immunoblotting, and immunohistochemistry were performed with the aim of characterizing the disease-causing variants. In case No.1, we...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861889/ https://www.ncbi.nlm.nih.gov/pubmed/31671693 http://dx.doi.org/10.3390/ijms20215418 |
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author | Malcher, Agnieszka Jedrzejczak, Piotr Stokowy, Tomasz Monem, Soroosh Nowicka-Bauer, Karolina Zimna, Agnieszka Czyzyk, Adam Maciejewska-Jeske, Marzena Meczekalski, Blazej Bednarek-Rajewska, Katarzyna Wozniak, Aldona Rozwadowska, Natalia Kurpisz, Maciej |
author_facet | Malcher, Agnieszka Jedrzejczak, Piotr Stokowy, Tomasz Monem, Soroosh Nowicka-Bauer, Karolina Zimna, Agnieszka Czyzyk, Adam Maciejewska-Jeske, Marzena Meczekalski, Blazej Bednarek-Rajewska, Katarzyna Wozniak, Aldona Rozwadowska, Natalia Kurpisz, Maciej |
author_sort | Malcher, Agnieszka |
collection | PubMed |
description | We analyzed three cases of Complete Androgen Insensitivity Syndrome (CAIS) and report three hitherto undisclosed causes of the disease. RNA-Seq, Real-timePCR, Western immunoblotting, and immunohistochemistry were performed with the aim of characterizing the disease-causing variants. In case No.1, we have identified a novel androgen receptor (AR) mutation (c.840delT) within the first exon in the N-terminal transactivation domain. This thymine deletion resulted in a frameshift and thus introduced a premature stop codon at amino acid 282. In case No.2, we observed a nonsynonymous mutation in the ligand-binding domain (c.2491C>T). Case No.3 did not reveal AR mutation; however, we have found a heterozygous mutation in CYP11A1 gene, which has a role in steroid hormone biosynthesis. Comparative RNA-Seq analysis of CAIS and control revealed 4293 significantly deregulated genes. In patients with CAIS, we observed a significant increase in the expression levels of PLCXD3, TM4SF18, CFI, GPX8, and SFRP4, and a significant decrease in the expression of SPATA16, TSACC, TCP10L, and DPY19L2 genes (more than 10-fold, p < 0.05). Our findings will be helpful in molecular diagnostics of patients with CAIS, as well as the identified genes could be also potential biomarkers for the germ cells differentiation process. |
format | Online Article Text |
id | pubmed-6861889 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-68618892019-12-05 Novel Mutations Segregating with Complete Androgen Insensitivity Syndrome and Their Molecular Characteristics Malcher, Agnieszka Jedrzejczak, Piotr Stokowy, Tomasz Monem, Soroosh Nowicka-Bauer, Karolina Zimna, Agnieszka Czyzyk, Adam Maciejewska-Jeske, Marzena Meczekalski, Blazej Bednarek-Rajewska, Katarzyna Wozniak, Aldona Rozwadowska, Natalia Kurpisz, Maciej Int J Mol Sci Article We analyzed three cases of Complete Androgen Insensitivity Syndrome (CAIS) and report three hitherto undisclosed causes of the disease. RNA-Seq, Real-timePCR, Western immunoblotting, and immunohistochemistry were performed with the aim of characterizing the disease-causing variants. In case No.1, we have identified a novel androgen receptor (AR) mutation (c.840delT) within the first exon in the N-terminal transactivation domain. This thymine deletion resulted in a frameshift and thus introduced a premature stop codon at amino acid 282. In case No.2, we observed a nonsynonymous mutation in the ligand-binding domain (c.2491C>T). Case No.3 did not reveal AR mutation; however, we have found a heterozygous mutation in CYP11A1 gene, which has a role in steroid hormone biosynthesis. Comparative RNA-Seq analysis of CAIS and control revealed 4293 significantly deregulated genes. In patients with CAIS, we observed a significant increase in the expression levels of PLCXD3, TM4SF18, CFI, GPX8, and SFRP4, and a significant decrease in the expression of SPATA16, TSACC, TCP10L, and DPY19L2 genes (more than 10-fold, p < 0.05). Our findings will be helpful in molecular diagnostics of patients with CAIS, as well as the identified genes could be also potential biomarkers for the germ cells differentiation process. MDPI 2019-10-30 /pmc/articles/PMC6861889/ /pubmed/31671693 http://dx.doi.org/10.3390/ijms20215418 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Malcher, Agnieszka Jedrzejczak, Piotr Stokowy, Tomasz Monem, Soroosh Nowicka-Bauer, Karolina Zimna, Agnieszka Czyzyk, Adam Maciejewska-Jeske, Marzena Meczekalski, Blazej Bednarek-Rajewska, Katarzyna Wozniak, Aldona Rozwadowska, Natalia Kurpisz, Maciej Novel Mutations Segregating with Complete Androgen Insensitivity Syndrome and Their Molecular Characteristics |
title | Novel Mutations Segregating with Complete Androgen Insensitivity Syndrome and Their Molecular Characteristics |
title_full | Novel Mutations Segregating with Complete Androgen Insensitivity Syndrome and Their Molecular Characteristics |
title_fullStr | Novel Mutations Segregating with Complete Androgen Insensitivity Syndrome and Their Molecular Characteristics |
title_full_unstemmed | Novel Mutations Segregating with Complete Androgen Insensitivity Syndrome and Their Molecular Characteristics |
title_short | Novel Mutations Segregating with Complete Androgen Insensitivity Syndrome and Their Molecular Characteristics |
title_sort | novel mutations segregating with complete androgen insensitivity syndrome and their molecular characteristics |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861889/ https://www.ncbi.nlm.nih.gov/pubmed/31671693 http://dx.doi.org/10.3390/ijms20215418 |
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