DHX37 Molecular Analysis in 46,XY Partial Gonadal Dysgenesis and Testicular Regression Syndrome

Abstract

Conditions that present atypical genital and / or gonadal development leading to a disagreement among genetic, gonadal and phenotypic sex are classified as Disorders of Sex Development (DSD). Several genes are known to act in the pathways of sex determination and differentiation, such as: WT1, SRY, NR5A1, DMRT1, SOX9, GATA4, NR0B1, HAM, AR, SRD5A2, HSD17B3, among others. Recently, three independent research groups identified pathogenic variants whithin DHX37 gene, which had not been previously associated with any sexual differentiation disorder. Such findings allowed relating DHX37 gene to 46,XY gonadal dysgenesis and testicular regression syndrome. DHX37 is a member of the large DEAH family of proteins and encodes an RNA helicase, which is essential for ribosome biogenesis. This enzyme is expressed in Leydig cells at different stages of maturation. Until now, only ten variations were identified in this gene, in a higher frequency of 46,XY DSD patients. Thus, the main goal of this project is to perform a molecular screening of the DHX37 gene in a cohort of twenty 46,XY patients diagnosed with gonadal dysgenesis or testicular regression syndrome, aiming to identify variants that can be related to the patients' phenotype.