ArticleEndocrine connections2021
The evolving role of whole-exome sequencing in the management of disorders of sex development.
Article in Endocrine connections, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 4 of them syntheses that pooled it.
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Who cites it
14 citing papers in PubMed, 4 syntheses or guidelines pooled it, 22 citations in OpenAlex.
- 46,XY DSD with Partial Gonadal Dysgenesis and Growth Failure in a Patient with 3q27.1 Microdeletion: Candidate Gene Curation After Exhaustive Literature Review.International journal of molecular sciences · 2026Pooled it
- Case Report: Integrating clinical presentation and genetic analysis in P450 oxidoreductase deficiency: a novel mutation and systematic review.Frontiers in endocrinology · 2026Pooled it
- Congenital adrenal hyperplasia, disorders of sex development, and infertility in patients with POR gene pathogenic variants: a systematic review of the literature.Journal of endocrinological investigation · 2023Pooled it
- Prevalence and Clustering of Congenital Heart Defects Among Boys With Hypospadias.JAMA network open · 2022Pooled it
- Spectrum and genotype-phenotype correlation of NR5A1 variants in 46,XY DSD: a systematic review and meta-analysis.Endocrine connections · 2026Article
- The potential of deep learning on the discovery of new genes implicated in differences of sex development.Computational and structural biotechnology journal · 2026Article
- Achieving an optimal pregnancy outcome through the combined utilization of micro-TESE and ICSI in cryptorchidism associated with a non-canonical splicing variant in RXFP2.Journal of assisted reproduction and genetics · 2024Article
- Identification and functional analysis of a rare variant of gene DHX37 in a patient with 46,XY disorders of sex development.Molecular genetics & genomic medicine · 2024Article
- [Hormonal and genetic causes of cryptorchidism].Problemy endokrinologii · 2023Article
- Current perspectives in hypospadias research: A scoping review of articles published in 2021 (Review).Experimental and therapeutic medicine · 2023Article
- Anomalies in Human Sex Determination: Usefulness of a Combined Cytogenetic Approach to Characterize an Additional Case with Xp Functional Disomy Associated with 46,XY Gonadal DysgenesisJournal of clinical research in pediatric endocrinology · 2023Article
- Transposable elements acquire time- and sex-specific transcriptional and epigenetic signatures along mouse fetal gonad development.Frontiers in cell and developmental biology · 2023Article
- Cis-Regulatory Control of Mammalian Sex Determination.Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation · 2021Review
- Patients with genital ambiguity referred without a sex definition: the relationship between clinical picture and defined sex of rearing.Jornal de pediatriaArticle
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveDisorders of sex development (DSD) are defined as congenital conditions in which the development of chromosomal, gonadal and anatomical sex is atypical. Despite wide laboratory and imaging investigations, the etiology of DSD is unknown in over 50% of patients.
methodsWe evaluated the etiology of DSD by whole-exome sequencing (WES) at a mean age of 10 years in nine patients for whom extensive evaluation, including hormonal, imaging and candidate gene approaches, had not identified an etiology.
resultsThe eight 46,XY patients presented with micropenis, cryptorchidism and hypospadias at birth and the 46,XX patient presented with labia majora fusion. In seven patients (78%), pathogenic variants were identified for RXFP2, HSD17B3, WT1, BMP4, POR, CHD7 and SIN3A. In two atients, no causative variants were found. Mutations in three genes were reported previously with different phenotypes: an 11-year-old boy with a novel de novo variant in BMP4; such variants are mainly associated with microphthalmia and in few cases with external genitalia anomalies in males, supporting the role of BMP4 in the development of male external genitalia; a 12-year-old boy with a known pathogenic variant in RXFP2, encoding insulin-like 3 hormone receptor, and previously reported in adult men with cryptorchidism; an 8-year-old boy with syndromic DSD had a de novo deletion in SIN3A.
conclusionsOur findings of molecular etiologies for DSD in 78% of our patients indicate a major role for WES in early DSD diagnosis and management - and highlights the importance of rapid molecular diagnosis in early infancy for sex of rearing decisions.
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