Role of chromosomal imbalances in the pathogenesis of DSD: A retrospective analysis of 115 prenatal samples

Differences of sex development (DSDs) are a group of congenital conditions characterized by a discrepancy between chromosomal, gonadal, and genital sex development of an individual, with significant impact on medical, psychological and reproductive life. The genetic heterogeneity of DSDs complicates...

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Veröffentlicht in:European journal of medical genetics 2023-06, Vol.66 (6), p.104748-104748, Article 104748
Hauptverfasser: Mary, L., Fradin, M., Pasquier, L., Quelin, C., Loget, P., Le Lous, M., Le Bouar, G., Nivot-Adamiak, S., Lokchine, A., Dubourg, C., Jauffret, V., Nouyou, B., Henry, C., Launay, E., Odent, S., Jaillard, S., Belaud-Rotureau, M.A.
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container_issue 6
container_start_page 104748
container_title European journal of medical genetics
container_volume 66
creator Mary, L.
Fradin, M.
Pasquier, L.
Quelin, C.
Loget, P.
Le Lous, M.
Le Bouar, G.
Nivot-Adamiak, S.
Lokchine, A.
Dubourg, C.
Jauffret, V.
Nouyou, B.
Henry, C.
Launay, E.
Odent, S.
Jaillard, S.
Belaud-Rotureau, M.A.
description Differences of sex development (DSDs) are a group of congenital conditions characterized by a discrepancy between chromosomal, gonadal, and genital sex development of an individual, with significant impact on medical, psychological and reproductive life. The genetic heterogeneity of DSDs complicates the diagnosis and almost half of the patients remains undiagnosed. In this context, chromosomal imbalances in syndromic DSD patients may help to identify new genes implicated in DSDs. In this study, we aimed at describing the burden of chromosomal imbalances including submicroscopic ones (copy number variants or CNVs) in a cohort of prenatal syndromic DSD patients, and review their role in DSDs. Our patients carried at least one pathogenic or likely pathogenic chromosomal imbalance/CNV or low-level mosaicism for aneuploidy. Almost half of the cases resulted from an unbalanced chromosomal rearrangement. Chromosome 9p/q, 4p/q, 3q and 11q anomalies were more frequently observed. Review of the literature confirmed the causative role of CNVs in DSDs, either in disruption of known DSD-causing genes (SOX9, NR0B1, NR5A1, AR, ATRX, …) or as a tool to suspect new genes in DSDs (HOXD cluster, ADCY2, EMX2, CAMK1D, …). Recurrent CNVs of regulatory elements without coding sequence content (i.e. duplications/deletions upstream of SOX3 or SOX9) confirm detection of CNVs as a mean to explore our non-coding genome. Thus, CNV detection remains a powerful tool to explore undiagnosed DSDs, either through routine techniques or through emerging technologies such as long-read whole genome sequencing or optical genome mapping.
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ispartof European journal of medical genetics, 2023-06, Vol.66 (6), p.104748-104748, Article 104748
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subjects Aneuploidy
Chromosomal imbalance
Chromosomes
CMA
CNV
DNA Copy Number Variations
DSD
Female
Genetics
Genital
Humans
Life Sciences
Mosaicism
Pregnancy
Prenatal
Prenatal Diagnosis - methods
Retrospective Studies
Translocation, Genetic
title Role of chromosomal imbalances in the pathogenesis of DSD: A retrospective analysis of 115 prenatal samples
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