Androgen receptor mRNA analysis from whole blood: a low-cost strategy for detection of androgen receptor gene splicing defects
| Autor: | Luciani R. Carvalho, Berenice B. Mendonca, Rafael Loch Batista, Sorahia Domenice, Andresa De Santi Rodrigues, Elaine Maria Frade Costa, Juliana M Silva, Mirian Yumie Nishi |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Silent mutation Male Genotype RNA Splicing Biology 03 medical and health sciences Exon SANGUE Genetics medicine Humans Genetic Predisposition to Disease RNA Messenger Gene Genetics (clinical) Alleles Genetic Association Studies Intron Exons Sequence Analysis DNA Androgen-Insensitivity Syndrome medicine.disease Molecular biology Introns Androgen receptor 030104 developmental biology Regulatory sequence Receptors Androgen RNA splicing Mutation Androgen insensitivity syndrome Cell-Free Nucleic Acids |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 1399-0004 |
| Popis: | Androgen insensitivity syndrome (AIS) is caused by defects in the androgen receptor (AR) gene and is the most common aetiology of 46,XY disorders of sex development. Allelic variants in the AR gene are found in 90% of complete AIS (CAIS), but in only 28% to 50% of cases of partial AIS. Even a single nucleic acid change can disrupt splicing sites or splicing regulatory sequences, resulting in inadequate exon and intron recognition, ultimately leading to an aberrant transcript. Therefore, we tested the feasibility of conducting AR cDNA analysis from whole blood and from gonadal tissue in a patient with CAIS due to AR synonymous mutation (c.1530C > T, p.Ser510Ser; NM_000044.3), which led to an aberrant splicing site causing deletion of 92 nucleotides resulting in a very short transcript. AR cDNA sequencing was similar in the whole blood and in the gonadal tissue, with similar evidence of a consequent altered AR transcript. We propose that analysis of AR RNA extracted from whole blood with AR DNA sequencing can help to improve the frequency of molecular diagnosis, particularly for partial AIS. |
| Databáze: | OpenAIRE |
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