Molecular and Cytogenetic Analysis of Romanian Patients with Differences in Sex Development.

Autor: Miclea D; Molecular Sciences Department, 'Iuliu Hatieganu' University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania.; Medical Genetics Department, Clinical Emergency Hospital for Children, 400370 Cluj-Napoca, Romania., Alkhzouz C; Medical Genetics Department, Clinical Emergency Hospital for Children, 400370 Cluj-Napoca, Romania.; Mother and Child Department, 'Iuliu Hatieganu' University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania., Bucerzan S; Medical Genetics Department, Clinical Emergency Hospital for Children, 400370 Cluj-Napoca, Romania.; Mother and Child Department, 'Iuliu Hatieganu' University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania., Grigorescu-Sido P; Mother and Child Department, 'Iuliu Hatieganu' University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania., Popp RA; Molecular Sciences Department, 'Iuliu Hatieganu' University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania., Pascanu IM; Endocrinology Department, George Emil Palade University of Medicine, Pharmacy, Science and Technology, 540142 Targu Mures, Romania., Cret V; Medical Genetics Department, Clinical Emergency Hospital for Children, 400370 Cluj-Napoca, Romania., Ghervan C; Endocrinology Department, 'Iuliu Hatieganu' University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania., Blaga L; Mother and Child Department, 'Iuliu Hatieganu' University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania., Zaharie G; Mother and Child Department, 'Iuliu Hatieganu' University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania.
Jazyk: angličtina
Zdroj: Diagnostics (Basel, Switzerland) [Diagnostics (Basel)] 2021 Nov 14; Vol. 11 (11). Date of Electronic Publication: 2021 Nov 14.
DOI: 10.3390/diagnostics11112107
Abstrakt: 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 + SRY testing. A high value of 17-hydroxyprogesterone was found in 39 patients, in whom strip assay analysis of the CYP21A2 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 CYP21A2 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 RSPO1 , FGFR1 , WT1 , CHD7 , AR , NIPBL , AMHR2 , AR , EMX2 , CYP17A1 , NR0B1 , GNRHR , GATA4 , and ATM genes.
Conclusion: An evaluation following a genetic testing protocol that included karyotype and SRY gene testing, CYP21A2 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.
Databáze: MEDLINE
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