Genomics applied to the diagnosis of patients with Syndromic Disorders of Sexual Development

• Grant number: 25/10332-8
• Support Opportunities: Scholarships in Brazil - Master
• Start date: July 01, 2025
• End date: February 28, 2027
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Helena Fabbri Scallet
• Grantee: Gisele Neves Pap
• Host Institution: Centro de Biologia Molecular e Engenharia Genética (CBMEG). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 24/00196-7 - Investigating new processes in gonadal development, AP.JP

Abstract

Disorders/Differences of Sex Development (DSD) encompass a set of congenital conditions characterized by incomplete or disordered genital and/or gonadal development leading to a discordance between genetic, gonadal and phenotypic sex. Within the DSD, there is a group of patients who present, in addition to the ambiguous genitalia, some malformation, which may involve: intellectual disability or neuropsychomotor delay; presence of at least one major congenital anomaly or at least three minor ones; and/or, short stature or weight-height deficit. This group is classified as Syndromic DSD, and can affect individuals with both 46,XX and 46,XY karyotype. These patients are often neglected in molecular investigations, because, due to the various associated malformations, they are usually treated in different health services, which do not refer them for genetic analysis. Currently, there are known genes and chromosomal regions related to syndromic DSD, however, to date, there is no published study in the literature that specifically covers genomic investigation for this group. Thus, the objective of this project is to investigate point and structural variants, through the whole genome sequencing (WGS) of 20 patients without a defined diagnosis within the syndromic DSD group. With these results, we aim to have a better understanding of the molecular mechanisms that lead to such a condition, as well as to offer accurate genetic counseling for these patients and families, with better psychological and social adaptation.