Context: Disorders of sexual development (DSD) are those medical conditions with abnormalities of sex chromosomes, gonads, internal ducts or external genitalia. Sex determination and differentiation is a process under genetic control, only partially explained. Genetic testing and identification of a cause in DSD is essential for a precise diagnosis and correct management and also has an important psychosocial motivation.
Aim: To make a genomic analyse, using SNP array technology, of a group of Romanian patients with DSD, with the aim to identify the CNV (copy number variants).
Material and method: We analysed 17 patients diagnosed in Clinical Emergency Hospital for Children, Cluj-Napoca, for each of them being made the clinical exam, hormonal/biochemical investigations, anatomic evaluation, by ultrasounds, genitography, IRM or biopsy, caryotype and SRY, analysis of CYP21A2 gene by stripassay (if elevated 17OH-progesterone) or other individualised analysis depending on clinical picture. For those patients without an obvious cause for DSD at clinical or paraclinical exam was done SNP array analysis using Infinium OmniExpress-24 BeadChip array (Illumina), the image acquisition being made by iScan System (Illumina). The data analysis was made using Genome Studio 3.0 and the CNV interpretation was made using: UCSC, DGV, Decipher, and OMIM databases.
Results and discussions: We identified 4/17 patients (23%) with pathogenic CNV or VOUS (variants of unknown significance). These CNV were: 10q26.3 duplication (121kb) in 2 patients, 16p11.2 duplication (597kb) and 6p21.33 homozygous deletion (1kb). Two CNV were considered pathogenic and two CNV were considered VOUS. Three patients presented a syndromic DSD and one an isolated DSD. In our country is the first group of DSD patients for whom we tried to go further with genetic testing, using a genomic approach. This genetic test permit to clarify the diagnosis in some cases and we hope to go further for unsolved cases, using the massively parallel sequencing. However, SNP array could be an analysis which can be useful in etiological diagnosis, especially in syndromic DSD.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology