High Molecular Diagnosis Rate in Undermasculinized Males with Differences in Sex Development Using a Stepwise Approach
| Autor: | John Gatti, Carol J Saunders, Anna Egan, Jill D. Jacobson, Julie Strickland, Emily G. Farrow, Laurel K. Willig, Leslie L. Heckert |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Adolescent Microarray Individual gene Disorders of Sex Development 030209 endocrinology & metabolism Sensitivity and Specificity 03 medical and health sciences 0302 clinical medicine Endocrinology Internal medicine Exome Sequencing Gene duplication medicine Humans Medical diagnosis Child Genetic testing Disorder of Sex Development 46 XY medicine.diagnostic_test business.industry Sexual Development Infant Newborn High-Throughput Nucleotide Sequencing Infant Karyotype Sex reversal 030104 developmental biology Child Preschool Karyotyping Female business Stepwise approach |
| Zdroj: | Endocrinology. 161 |
| ISSN: | 1945-7170 0013-7227 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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