Differences of Sex Development (DSD) are a group of conditions in which there is atypical anatomic, gonadal, or chromosomal sex. With input from multiple stakeholders, our laboratory recently validated a genetic testing panel for non-syndromic DSD, which utilizes targeted next generation sequencing and exon-level microarray analysis. Data from the first 37 consecutive tests is presented here. The majority of patients in this cohort were evaluated in our institution's DSD clinic, which includes providers specializing in pediatric and reproductive endocrinology, genetics, urology, gynecology and child and adolescent psychology. Almost all patients had prior karyotype, SRY FISH, and/or chromosomal microarray testing. Exclusion criteria for panel testing included the presence of syndromic features or suspected 21-hydryoxylase deficiency. Pathogenic or likely pathogenic variants in genes associated with dominant conditions were reported for 15 (40.5%) individuals. The pathogenic and likely pathogenic variants were identified in 10 different genes: AMH, AMHR2, ANOS1, AR (in 5 unrelated individuals), CYP17A1, MAMLD1 (in two unrelated individuals), MAP3K1, PROKR2, SRY, and STAR. For 3 other individuals (8%), a single pathogenic variant was reported in a gene associated with a recessive condition. Variants of uncertain clinical significance were reported for 5 individuals (13.5%), and no variants were reported for 14 individuals (38%). Close collaboration between the laboratory and the clinical team during the test validation process, as well as ongoing discussions surrounding test utilization, enabled development of a panel most appropriate for our patient population, with a high diagnostic rate. The targeted panel approach avoided issues related to incidental findings and contributed to the lower rate of reported variants of uncertain significance. Future goals for the DSD panel include streamlining the laboratory workflow and regular updates to panel content to include genes recently implicated in DSD-related conditions.

To read this article in full you will need to make a payment

DOI: https://doi.org/10.1016/j.cancergen.2022.05.035

© 2022 Published by Elsevier Inc.