Cytogenomic investigation of syndromic Brazilian patients with differences of sexual development

Abstract Background: Molecular biology and cytogenomics methods have gained space in the clinical investigation for patients with disorders/differences in sexual development (DSD). Here we aimed to evaluate the role of SNP-array in achieving a molecular diagnosis in a sample of 22 Brazilian patients with syndromic DSD of unknown etiology, and to compare the relationship between the clinical diagnosis and the SNP-array results.Methods: 22 patients with DSD associated with syndromic features in several systems other than the genital tract were included in the study and underwent search for genomic copy number variations (CNVs) by SNP-array.Results: In two patients, the diagnosis of 46,XX SRY+ DSD was established. Additionally, two deletions were revealed (3q29 and Xp22.33), justifying the syndromic phenotype in these patients. Two pathogenic CNVs, a 10q25.3-q26.2 and 13q33.1 deletion encompassing the FGFR2 and the EFNB2 gene were associated with genital atypia and syndromic characteristics in two patients with 46, XY DSD. In a third 46,XY DSD patient, we identified a duplication in the 14q11.2-q12 region of 6.5 Mb associated with a deletion in the 21p11.2-q21.3 region of 12.7Mb. In a 46,XY DSD patient with delayed neuropsychomotor development and congenital cataract, a 12Kb deletion on chromosome 10 was found, justifying the congenital cataract.Conclusions: The SNP-array technique identified the molecular etiology in 40% (2/5) of patients with 46,XX DSD and 17.6% (3/17) of patients with 46,XY DSD. In one patient the array contributed to partially clarify the patient's syndromic phenotype, but not the genital atypia.