Variants of and May Contribute Towards the Broad Phenotype Observed in 46,XY DSD Patients with Heterozygous Variants of

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2020 Nov 18

PMID 33202802

Citations 6

Authors

Idoia Martinez de Lapiscina

Rana Aa Mahmoud

Kay-Sara Sauter

Isabel Esteva

Milagros Alonso

Ines Costa

Jose Manuel Rial-Rodriguez

Amaia Rodriguez-Estevez

Amaia Vela

Luis Castano

Christa E Fluck

Affiliations

Soon will be listed here.

Abstract

Variants of are often found in individuals with 46,XY disorders of sex development (DSD) and manifest with a very broad spectrum of clinical characteristics and variable sex hormone levels. Such complex phenotypic expression can be due to the inheritance of additional genetic hits in DSD-associated genes that modify sex determination, differentiation and organ function in patients with heterozygous variants. Here we describe the clinical, biochemical and genetic features of a series of seven patients harboring monoallelic variants in the gene. We tested the transactivation activity of novel variants. We additionally included six of these patients in a targeted diagnostic gene panel for DSD and identified a second genetic hit in known DSD-causing genes , and in three individuals. Our study increases the number of variants related to 46,XY DSD and supports the hypothesis that a digenic mode of inheritance may contribute towards the broad spectrum of phenotypes observed in individuals with a heterozygous variation.

Citing Articles

Novel Gene Variants in a Nationwide Cohort of Patients with Pheochromocytoma and Paraganglioma.

Martinez de Lapiscina I, Diego E, Baquero C, Fernandez E, Menendez E, Moure M Int J Mol Sci. 2024; 25(22).

PMID: 39596125 PMC: 11593415. DOI: 10.3390/ijms252212056.

/SF-1 Collaborates with Inhibin α and the Androgen Receptor.

Elzenaty R, Kouri C, Martinez de Lapiscina I, Sauter K, Moreno F, Camats-Tarruella N Int J Mol Sci. 2024; 25(18).

PMID: 39337600 PMC: 11432463. DOI: 10.3390/ijms251810109.

Characterization of 35 Novel NR5A1/SF-1 Variants Identified in Individuals With Atypical Sexual Development: The SF1next Study.

Elzenaty R, Martinez de Lapiscina I, Kouri C, Sauter K, Sommer G, Castano L J Clin Endocrinol Metab. 2024; 110(3):e675-e693.

PMID: 38623954 PMC: 11834716. DOI: 10.1210/clinem/dgae251.

Clinical and genetic characteristics of a large international cohort of individuals with rare NR5A1/SF-1 variants of sex development.

Kouri C, Sommer G, Martinez de Lapiscina I, Elzenaty R, Tack L, Cools M EBioMedicine. 2024; 99:104941.

PMID: 38168586 PMC: 10797150. DOI: 10.1016/j.ebiom.2023.104941.

Genetic reanalysis of patients with a difference of sex development carrying the NR5A1/SF-1 variant p.Gly146Ala has discovered other likely disease-causing variations.

Martinez de Lapiscina I, Kouri C, Aurrekoetxea J, Sanchez M, Elzenaty R, Sauter K PLoS One. 2023; 18(7):e0287515.

PMID: 37432935 PMC: 10335684. DOI: 10.1371/journal.pone.0287515.

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