46,XY disorders of sex development: the use of NGS for prevalent variants

Human Genetics, Journal Year: 2022, Volume and Issue: 141(12), P. 1863 - 1873

Published: June 21, 2022

Language: Английский

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Individuals with numerical and structural variations of sex chromosomes: interdisciplinary management with focus on fertility potential

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: May 5, 2023

Diagnosis and management of individuals who have differences sex development (DSD) due to numerical or structural variations chromosomes (NSVSC) remains challenging. Girls Turner syndrome (45X) may present with varying phenotypic features, from classical/severe minor, some remain undiagnosed. Boys girls 45,X/46,XY chromosomal mosaicism syndrome-like features short stature; therefore, unexplained stature during childhood requires karyotype analysis in both sexes, particularly if characteristic atypical genitalia are present. Many Klinefelter (47XXY) undiagnosed only diagnosed as adults fertility problems. Newborn screening by heel prick tests could potentially identify chromosome but would ethical financial implications, in-depth cost-benefit analyses needed before nationwide can be introduced. Most NSVSC lifelong co-morbidities healthcare should holistic, personalized centralized, a focus on information, psychosocial support shared decision-making. Fertility potential assessed individually discussed at an appropriate age. Oocyte ovarian tissue cryopreservation is possible women live births been reported following assisted reproductive technology (ART). Testicular sperm cell extraction (TESE) men mosaicism, there no established protocol fathering children. Some now father child TESE ART, multiple reports healthy births. Children NSVSC, their parents DSD team members need address possibilities questions relating preservation, guidelines international studies still needed.

Language: Английский

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Next-Generation Sequencing as First-Line Diagnostic Test in Patients With Disorders of Sex Development?

The Journal of Clinical Endocrinology & Metabolism, Journal Year: 2022, Volume and Issue: 107(6), P. e2628 - e2629

Published: March 7, 2022

Disorders of sex development (DSD) are a group highly heterogeneous disorders presenting mainly at birth or pubertal age, characterized by discordance between chromosomal, gonadal, and/or genital sex. Newborns usually present with ambiguous genitalia while adolescents atypical downright absent (1). The underlying pathogenesis may rely on gonadal differentiation hormone biosynthesis action. Indeed, the pioneering experiments performed Alfred Jost in 1940s demonstrated that actions 2 testicular hormones—androgens and subsequently anti-Müllerian (AMH)—are essential for virilization fetus, absence hormones fetal undertake female pathway (2). primordia external identical all embryos before differentiation, their degree during life depends extent androgen This can be clinically assessed using score, based standardized description genitalia, which applies graded scale from (score 0) to male 10.5-12), intermediate values patients (3). occur individuals chromosomes but also as consequence single gene variants, particularly 46,XY patients. Isolated impaired testosterone dihydrotestosterone (DHT) target-organ insensitivity androgens other endocrine etiologies DSD, resulting mutations (4). Atypical, rather than ambiguous, characteristic complex dysmorphic syndromes not endocrine-related prompt different diagnostic approach (5).

Language: Английский

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Whole genome sequencing identifies a missense polymorphism in PADI6 associated with testicular/ovotesticular XX disorder of sex development in dogs

Genomics, Journal Year: 2022, Volume and Issue: 114(4), P. 110389 - 110389

Published: May 18, 2022

Disorders of sex development (DSDs) are congenital malformations defined as discrepancies between chromosomes and phenotypical sex. Testicular or ovotesticular XX DSDs frequently observed in female dogs, while monogenic XY less frequent. Here, we applied whole genome sequencing (WGS) to search for causative mutations DSD females French Bulldogs (FB) American Staffordshire Terries (AST) Yorkshire (YT). The WGS results were validated by Sanger ddPCR. It was shown that a missense SNP the PADI6 gene, is significantly associated with (SRY-negative) phenotype AST (P = 0.0051) FB 0.0306). On contrary, did not find any variant YTs. Our study suggests genetic background may be more complex breed-specific.

Language: Английский

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Sex-determining 3D regulatory hubs revealed by genome spatial auto-correlation analysis

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Nov. 18, 2022

ABSTRACT Mammalian sex is determined by opposing networks of ovarian and testicular genes that are well characterized. However, its epigenetic regulation still largely unknown, thus limiting our understanding a fundamental process for species propagation. Here we explore the 3D chromatin landscape determination in vivo , profiling FACS-sorted embryonic mouse gonadal populations, prior after determination, both sexes. We integrate Hi-C with ChIP-seq experiments using METALoci novel genome spatial auto-correlation analysis identifies enhancer hubs across genome. uncover prominent rewiring interactions during affecting hundreds display temporal- sex-specific expression. Moreover, identification allows reconstruction regulatory networks, revealing key transcription factors involved determination. By combining predictive approaches validations transgenic mice identify Fgf9 hub, deletion which results male-to-female reversal upregulation ovarian-specific markers initiation meiosis. Thus, an effective strategy to associated biological processes further characterize functional role

Language: Английский

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