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- Title
Molecular and Cytogenetic Analysis of Romanian Patients with Differences in Sex Development.
- Authors
Miclea, Diana; Alkhzouz, Camelia; Bucerzan, Simona; Grigorescu-Sido, Paula; Popp, Radu Anghel; Pascanu, Ionela Maria; Cret, Victoria; Ghervan, Cristina; Blaga, Ligia; Zaharie, Gabriela
- Abstract
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.
- Subjects
SEX chromosome abnormalities; GENETIC variation; Y chromosome; NUCLEOTIDE sequencing; HOSPITAL emergency services; GENETIC testing
- Publication
Diagnostics (2075-4418), 2021, Vol 11, Issue 11, p2107
- ISSN
2075-4418
- Publication type
Article
- DOI
10.3390/diagnostics11112107