Oligogenic Origin of Differences of Sex Development in Humans

International Journal of Molecular Sciences
Nuria CamatsLaura Audi

Abstract

Sex development is a very complex biological event that requires the concerted collaboration of a large network of genes in a spatial and temporal correct fashion. In the past, much has been learned about human sex development from monogenic disorders/differences of sex development (DSD), but the broad spectrum of phenotypes in numerous DSD individuals remains a conundrum. Currently, the genetic cause of less than 50% of DSD individuals has been solved and oligogenic disease has been proposed. In recent years, multiple genetic hits have been found in individuals with DSD thanks to high throughput sequencing. Our group has been searching for additional genetic hits explaining the phenotypic variability over the past years in two cohorts of patients: 46,XY DSD patients carriers of NR5A1 variants and 46,XY DSD and 46,XX DSD with MAMLD1 variants. In both cohorts, our results suggest that the broad phenotypes may be explained by oligogenic origin, in which multiple hits may contribute to a DSD phenotype, unique to each individual. A search for an underlying network of the identified genes also revealed that a considerable number of these genes showed interactions, suggesting that genetic variations in these genes may affect sex deve...Continue Reading

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Citations

Nov 8, 2020·Journal of Clinical Medicine·Pedro Acién, Maribel Acién
Dec 4, 2020·International Journal of Molecular Sciences·Laura AudíChrista E Flück
Nov 19, 2020·International Journal of Molecular Sciences·Idoia Martínez de LaPiscinaChrista E Flück
May 14, 2021·The Journal of Steroid Biochemistry and Molecular Biology·Sofia E LunaJennifer A Wambach
May 11, 2021·Frontiers in Pediatrics·Silvano BertelloniDiego G Peroni
Oct 16, 2021·Current Opinion in Pediatrics·Idoia Martinez de LaPiscina, Christa E Flück

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Methods Mentioned

BETA
exome sequencing

Software Mentioned

STRING
MutationTaster
ExomeDepth
SIFT

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