Molecular and Cytogenetic Analysis of Romanian Patients with Differences in Sex Development
Differences in sex development (DSD) are often correlated with a genetic etiology. This study aimed to assess the etiology of DSD patients following a protocol of genetic testing. Materials and methods. This study prospectively investigated a total of 267 patients with DSD who presented to Clinical...
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| Autores principales: | , , , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/3ba310ab17c9459a953f27c59e2db6be |
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| Sumario: | Differences in sex development (DSD) are often correlated with a genetic etiology. This study aimed to assess the etiology of DSD patients following a protocol of genetic testing. Materials and methods. This study prospectively investigated a total of 267 patients with DSD who presented to Clinical Emergency Hospital for Children Cluj-Napoca between January 2012 and December 2019. Each patient was clinically, biochemically, and morphologically evaluated. As a first intervention, the genetic test included karyotype + <i>SRY</i> testing. A high value of 17-hydroxyprogesterone was found in 39 patients, in whom strip assay analysis of the <i>CYP21A2</i> gene was subsequently performed. A total of 35 patients were evaluated by chromosomal microarray technique, and 22 patients were evaluated by the NGS of a gene panel. Results. The karyotype analysis established the diagnosis in 15% of the patients, most of whom presented with sex chromosome abnormalities. Genetic testing of <i>CYP21A2</i> established a confirmation of the diagnosis in 44% of patients tested. SNP array analysis was particularly useful in patients with syndromic DSD; 20% of patients tested presented with pathogenic CNVs or uniparental disomy. Gene panel sequencing established the diagnosis in 11 of the 22 tested patients (50%), and the androgen receptor gene was most often involved in these patients. The genes that presented as pathogenic or likely pathogenic variants or variants of uncertain significance were <i>RSPO1</i>, <i>FGFR1</i>, <i>WT1</i>, <i>CHD7</i>, <i>AR</i>, <i>NIPBL</i>, <i>AMHR2</i>, <i>AR</i>, <i>EMX2</i>, <i>CYP17A1</i>, <i>NR0B1</i>, <i>GNRHR</i>, <i>GATA4</i>, and <i>ATM</i> genes. Conclusion. An evaluation following a genetic testing protocol that included karyotype and <i>SRY</i> gene testing, <i>CYP21A2</i> analysis, chromosomal analysis by microarray, and high-throughput sequencing were useful in establishing the diagnosis, with a spectrum of diagnostic yield depending on the technique (between 15 and 50%). Additionally, new genetic variants not previously described in DSD were observed. |
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