Genetic and Clinical Characteristics of 185 Japanese Children with 46,XY Differences of Sex Development.

Autor:	Hayashi M; Department of Pediatrics, Keio University School of Medicine, Tokyo 160-8582, Japan., Narumi S; Department of Pediatrics, Keio University School of Medicine, Tokyo 160-8582, Japan.; Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan., Sato T; Department of Pediatrics, Keio University School of Medicine, Tokyo 160-8582, Japan., Amano N; Department of Pediatrics, Keio University School of Medicine, Tokyo 160-8582, Japan., Suwanai AS; Department of Pediatrics, Keio University School of Medicine, Tokyo 160-8582, Japan., Haruna H; Department of Pediatrics and Adolescent Medicine, Juntendo University School of Medicine, Tokyo 113-8421, Japan., Muroya K; Department of Endocrinology and Metabolism, Kanagawa Children's Medical Center, Yokohama 232-8555, Japan., Adachi M; Department of Endocrinology and Metabolism, Kanagawa Children's Medical Center, Yokohama 232-8555, Japan., Asanuma H; Department of Urology, Keio University School of Medicine, Tokyo 160-8582, Japan., Ohashi H; Division of Medical Genetics, Saitama Children's Medical Center, Saitama 330-8777, Japan., Ishii T; Department of Pediatrics, Keio University School of Medicine, Tokyo 160-8582, Japan., Hasegawa T; Department of Pediatrics, Keio University School of Medicine, Tokyo 160-8582, Japan.
Jazyk:	angličtina
Zdroj:	The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2024 Nov 21. Date of Electronic Publication: 2024 Nov 21.
DOI:	10.1210/clinem/dgae813
Abstrakt:	Context: 46,XY differences of sex development (DSD) are heterogeneous in etiology. The detailed phenotypes of 46,XY DSD patients with monogenic disorders have not been fully elucidated. Objectives: To estimate the proportion of monogenic disorders in 46,XY DSD and to characterize the clinical phenotypes of patients with monogenic disorders. Methods: A total of 185 Japanese patients (178 families) were enrolled. We sequenced 25 genes related to 46,XY DSD, and assessed the pathogenicity of the identified sequence variants according to the American College of Medical Genetics and Genomics guidelines, supplemented by in silico or in vitro analyses. We analyzed the clinical phenotypes of patients with monogenic disorders, with particular attention to the external or internal genitalia. Results: We identified 51 patients (47 families) with any monogenic disorders (26%), who possessed pathogenic variants in AR (11%), SRD5A2 (4.5%), NR5A1 (4.0%), SRY (2.8%), WT1 (1.1%), STAR (1.1%), CYP17A1 (0.56%), HSD3B2 (0.56%), or MAP3K1 (0.56%). The proportion of monogenic disorders was significantly higher in subjects with detected Müllerian derivatives (57%) than in those undetected (26%) (P = 0.029), in subjects with female-typical genitalia (91%) than those with ambiguous genitalia (19%) (P < 0.001). Conclusions: The proportion of monogenic disorders in Japanese 46,XY DSD patients was approximately 26%. Monogenic disorders were frequent among patients with severe undermasculinization of the external or internal genitalia. (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)
Databáze:	MEDLINE
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