Molecular study of developmental sex disorders in children

Abstract

Background: Sex determination and differentiation in humans are processes that involve
the interaction of several genes such as SRY, SOX9 genes which are important in the development of the male genital system. Also NR5A1 gene plays an important role in the development of gonads and the adrenal glands. Aim of the study include clinical assessment of children with disorders of sex development, molecular analyses for SRY, SOX9 and NR5A1 genes and genetic counseling for the patients and their families.
Subjects and methods: This study included sixteen patients from 1 day to 6 years old attending the Genetics and Endocrinology unit, Pediatric department, Faculty of Medicine, Menoufiya University, Egypt. All cases were subjected to: detailed history, thorough clinical examination, routine and hormonal investigations, imaging studies, cytogenetic and molecular studies for SRY, SOX9 and NR5A1 genes.
Results: Positive consanguinity between the parents was detected in seven patients (43.75%). Serum 17 OH progesterone was elevated in five patients (31.25%) and below normal ranges in two patients (12.5%). Cytogenetic study revealed six patients with normal (46, XX) karyotype, eight patients with normal (46, XY) karyotype, one patient had (45, X) karyotype and another with (45, X/46, XY) karyotype. Thirteen out of sixteen patients undergone molecular studies, SRY gene was +ve for six patients with normal male (46, XY) undergone and one patient with (45, X) karyotype (translocated SRY). SRY was ve for five patients with normal female (46, XX) karyotype and one patient with (45, X/46, XY) karyotype (deleted SRY). All patients were +ve for SOX9 and NR5A1 genes and no deletions detected.
Conclusion: Genetic studies beside clinical and hormonal evaluation will allow us to rapidly
reach a diagnosis and to identify a ‘molecular sex’ for each patient.

KEYWORDS DSD; Ambiguous genitalia; SRY; SOX9; NR5A1; Genetic counseling