Cytogenetic and molecular study in intersex

“Disorders of Sex Development” (DSD) is the state of a person whose sex chromosomes, genitalia and/or secondary sex characteristics are determined to be neither exclusively male nor female. The aim of this work was the genetic study of patients with ambiguous genitalia and genetic counseling of these cases. This study was conducted in the period from November 2007 to February 2009. Cases were obtained from the Genetics and Endocrine Units, Pediatric department, Faculty of Medicine, Menoufiya University, Egypt. Thirteen cases with ambiguous genitalia were studied, 10 genetic female and 3 genetic male patients. Their ages ranged from the first week to eight years. All cases were subjected to the following: Detailed history, thorough clinical examination, routine investigations, hormonal, imaging studies, cytogenetic study and molecular study. Sequencing for both the SRY and the CYP21 genes and genetic counseling were performed. Study revealed that among our patients, cases number 2 and 11 were mainly presented as salt losing crisis. Cases 5 and 13 were presented with hirsutism of the external genitalia and upper and lower limbs. Eight cases (61.5%) had a positive consanguinity and Cases 3 and 4 were sisters. Hormonal study revealed that (adrenocorticotropic hormone) ACTH, was within the normal range with a mean 83.14 pg/ml ± 53.6 pg/ml for all patients. Serum Cortisol and 17-OHP (17-hydroxyprogesterone) were elevated in all patients. Karyotype using G-banding showed that there were no apparent anomalies in the sex chromosomes. We found four cases (30.8%) with different mutations in the SRY gene at codon Q57R and S143C. As for the CYP21 gene, we found a variety of deletions in size and site within the structure of the gene in 85.4% of cases leading to alteration in the function of the CYP21 gene which ultimately lead to congenital adrenal hyperplasia (CAH) in these cases.