ESPE Abstracts

Introduction: Microarray (SNP array) method offers a powerful full genome scanning opportunity in the diagnosis of disorders of sex development (DSD).

Aim and Method: We aimed to determine the copy number variations (CNVs) by using the microarray method to elucidate the molecular etiology in DSD patients. The variants found were scored according to the American College of Medical Genetics and Genomics criteria.

Results: Twenty-two cases with no molecular genetic etiology and no chromosomal anomaly were included in the study. Eighteen (81.8%) of the cases were classified as 46,XY, and 4 (18.1%) as 46,XX DSD. The age of admission was 7.44 months (4 days-15 years). In the 46,XX DSD patient group, 2 (%50) patients were followed up with a preliminary diagnosis of gonadal dysgenesis, 2 (%50) patients with androgen excess. In the 46,XY DSD group, 6 (33.3%), patients were followed up with a preliminary diagnosis of androgen effect defect, 10 (55.5%) patients were followed up with androgen synthesis defect and 2 (11.1%) patients were followed up with gonadal dysgenesis. External genitalia score (EGS) of the patients in the 46,XY DSD group at the time of admission in 4 (22.2%) between 0-5; in 10 (55.5%) patients between 5-10 and in 4 (22.2%) patients was evaluated as 10 and above. Of 46,XX DSDs, 2 (50%) admitted with suspicious external genitalia, one (25%) primary amenorrhea and one (25%) coincidentally found Müllerian agenesis. There were consanguinity between the parents in four (18.1%) cases. While no variant was detected in 4 out of 22 cases with microarray analysis, a total of 142 copy number changes were detected in 18 cases. Of these, 114 (80.3%) were deletions and 28 (19.8%) were duplications. When variants of 18 cases with copy number changes were evaluated 13 out of 5 cases were pathogenic; 19 out of 5 cases were classified as undetermined. While only 1 of the variants classified as pathogenic had a hypospadias-related phenotype previously recorded in databases, no genital anomalies were reported in other variants.

Conclusion: Microarray analysis should be included in selected cases within the diagnostic approach to elucidate the molecular etiology of DSD cases. In addition, microarray analysis can guide studies to find new genes responsible for DSD.