Disorders of sex development (DSD) have defined as congenital conditions in which the development of chromosomal, gonadal, or anatomical sex is atypical. Wilms tumor 1(WT1) gene mutations have been described in 46,XY patients with ambiguous genitalia or complete gonadal dysgenesis with or without Wilms tumor, nephropathy, gonadoblastoma and other defects e.g. cryptorchidism, hypospadias. Sex chromosome mosaicism is a major cause of DSD with a wide phenotypic variability. The phenotype is primarily dependent on the proportion of each cell line in the developing gonads. This study reports one year old infant, reared as a male, presented with ambiguous genitalia. According to clinical investigations of the gonadal phenotype, gonadal histopathology and the karyotype, our patient was clinically diagnosed to have mixed gonadal dysgenesis (MGD). Furthermore, pelvic ultrasonography showed moderate pelvicalyceal dilatation in the left kidney. Cytogenetics studies have detected two cell lines by karyotype analysis of blood lymphocytes 45,X/46,X,idic(Y)(q11.2). FISH was also applied on gonadal cells and showed the same type of sex chromosome mosaicism, but with different distribution. Sequencing analysis of WT1 gene showed that the patient has a novel heterozygous missense mutation in exon 9. In silico functional studies predicted the pathogenicity of the mutation. This is the first study to report a mutation in WT1 in MGD patient. This study demonstrates the importance of WT1 in male sexual differentiation and kidney development.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology