High Molecular Diagnosis Rate in Undermasculinized Males with Differences in Sex Development Using a Stepwise Approach.

Autor:	Jacobson JD; Division of Endocrinology and Diabetes, Children's Mercy Hospitals and Clinics, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri., Willig LK; Division of Nephrology, Children's Mercy Hospitals and Clinics, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri.; Center for Pediatric Genomic Medicine Children's Mercy Hospitals and Clinics, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri., Gatti J; Division of Urology, Department of Surgery, Children's Mercy Hospitals and Clinics, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri., Strickland J; Division of Pediatric and Adolescent Gynecology, Department of Surgery, Children's Mercy Hospitals and Clinics, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri., Egan A; Developmental and Behavioral Sciences, Department of Pediatrics, Children's Mercy Hospitals and Clinics, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri., Saunders C; Center for Pediatric Genomic Medicine Children's Mercy Hospitals and Clinics, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri., Farrow E; Center for Pediatric Genomic Medicine Children's Mercy Hospitals and Clinics, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri., Heckert LL; Department of Molecular and Integrative Physiology, University of Kansas School of Medicine, Kansas City, Kansas.
Jazyk:	angličtina
Zdroj:	Endocrinology [Endocrinology] 2020 May 01; Vol. 161 (5).
DOI:	10.1210/endocr/bqz015
Abstrakt:	Differences of sex development (DSDs) are a constellation of conditions that result in genital ambiguity or complete sex reversal. Although determining the underlying genetic variants can affect clinical management, fewer than half of undermasculinized males ever receive molecular diagnoses. Next-generation sequencing (NGS) technology has improved diagnostic capabilities in several other diseases, and a few small studies suggest that it may improve molecular diagnostic capabilities in DSDs. However, the overall diagnostic rate that can be achieved with NGS for larger groups of patients with DSDs remains unknown. In this study, we aimed to implement a tiered approach to genetic testing in undermasculinized males seen in an interdisciplinary DSD clinic to increase the molecular diagnosis rate in this group. We determined the diagnosis rate in patients undergoing all clinically available testing. Patients underwent a stepwise approach to testing beginning with a karyotype and progressing through individual gene testing, microarray, panel testing, and then to whole-exome sequencing (WES) if no molecular cause was found. Deletion/duplication studies were also done if deletions were suspected. Sixty undermasculinized male participants were seen in an interdisciplinary DSD clinic from 2008 to 2016. Overall, 37/60 (62%) of patients with Y chromosomes and 46% of those who were 46XY received molecular diagnoses. Of the 46,XY patients who underwent all available genetic testing, 18/28 (64%) achieved molecular diagnoses. This study suggests that the addition of WES testing can result in a higher rate of molecular diagnoses compared to genetic panel testing. (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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