DHX37 and the Implications in Disorders of Sex Development: An Update Review

Abstract

<b><i>Background:</i></b> <i>DHX37</i> is an autosomal gene responsible for encoding a helicase from the DExD/H-box family that plays an essential role in ribosome biogenesis. Variants in this gene were previously reported in two different phenotypes: neurodevelopmental disorders and disorders/differences of sex development (DSD). Particularly for the DSD group, variants were mainly reported associated with gonadal dysgenesis and testicular regression syndrome. <b><i>Summary:</i></b> Focusing specifically in the DSD group, we revised the 21 <i>DHX37</i> variants described across a total of 55 cases published in the literature so far. We summarized the most important clinical and molecular features of all cases, trying to have a better comprehensiveness about this gene in the sexual development. <b><i>Key Messages:</i></b> The trick question regarding <i>DHX37</i> is how a helicase involved in basic cell function could have a specific role in testis development. Little is known about the impact of <i>DHX37</i> variants in DSD individuals. Nevertheless, current research strongly suggests that <i>DHX37</i> is involved in the male sex development pathway, particularly in testis determination and maintenance. This is evidenced by the predominant assignment of affected individuals as males and the presence of Wolffian structures in most of the cases. Advancements in molecular techniques, such as the generation of induced pluripotent stem cells and the digenic inheritance for <i>DHX37</i> cases, are also addressed in this paper. This represents the first comprehensive review of all <i>DHX37</i> variants published in the literature to date.