Next Article in Journal
Role of Non-Coding Variants in Brugada Syndrome
Previous Article in Journal
Phytopathogenic Cercosporoid Fungi—From Taxonomy to Modern Biochemistry and Molecular Biology
Previous Article in Special Issue
The FKBP4 Gene, Encoding a Regulator of the Androgen Receptor Signaling Pathway, Is a Novel Candidate Gene for Androgen Insensitivity Syndrome
Article

Variants of STAR, AMH and ZFPM2/FOG2 May Contribute towards the Broad Phenotype Observed in 46,XY DSD Patients with Heterozygous Variants of NR5A1

1
Biocruces Bizkaia Health Research Institute, Cruces University Hospital, UPV/EHU, CIBERER, CIBERDEM, ENDO-ERN. Plaza de Cruces 12, 48903 Barakaldo, Spain
2
Department of Pediatrics, Endocrinology Section, Ain Shams University, 38 Abbasia, Nour Mosque, El-Mohamady, Al Waili, Cairo 11591, Egypt
3
Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics, Department of BioMedical Research, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse 15, 3010 Bern, Switzerland
4
Endocrinology Section, Gender Identity Unit, Regional University Hospital of Malaga, Av. de Carlos Haya, s/n, 29010 Málaga, Spain
5
Pediatric Endocrinology Department, Ramon y Cajal University Hospital, Ctra. de Colmenar Viejo km. 9, 100, 28034 Madrid, Spain
6
Pediatric Department, Manises Hospital, Avda. Generalitat Valenciana 50, 46940 Manises, Spain
7
Pediatric Endocrinology Department, Nuestra Señora de Candelaria University Hospital, Ctra general del Rosario 145, 38010 Santa Cruz de Tenerife, Spain
8
Pediatric Endocrinology Department, Cruces University Hospital, Plaza de Cruces 12, 48903 Barakaldo, Spain
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(22), 8554; https://doi.org/10.3390/ijms21228554
Received: 3 October 2020 / Revised: 29 October 2020 / Accepted: 9 November 2020 / Published: 13 November 2020
(This article belongs to the Special Issue Sex Determination Mechanisms and Disease)
Variants of NR5A1 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 NR5A1 variants. Here we describe the clinical, biochemical and genetic features of a series of seven patients harboring monoallelic variants in the NR5A1 gene. We tested the transactivation activity of novel NR5A1 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 STAR, AMH and ZFPM2/FOG2 in three individuals. Our study increases the number of NR5A1 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 NR5A1 variation. View Full-Text
Keywords: disorder/difference of sex development; DSD; steroidogenic factor 1; NR5A1/SF1; STAR; AMH; FOG2; oligogenic disorders; genotype–phenotype correlation disorder/difference of sex development; DSD; steroidogenic factor 1; NR5A1/SF1; STAR; AMH; FOG2; oligogenic disorders; genotype–phenotype correlation
Show Figures

Figure 1

MDPI and ACS Style

Martínez de LaPiscina, I.; Mahmoud, R.A.; Sauter, K.-S.; Esteva, I.; Alonso, M.; Costa, I.; Rial-Rodriguez, J.M.; Rodríguez-Estévez, A.; Vela, A.; Castano, L.; Flück, C.E. Variants of STAR, AMH and ZFPM2/FOG2 May Contribute towards the Broad Phenotype Observed in 46,XY DSD Patients with Heterozygous Variants of NR5A1. Int. J. Mol. Sci. 2020, 21, 8554. https://doi.org/10.3390/ijms21228554

AMA Style

Martínez de LaPiscina I, Mahmoud RA, Sauter K-S, Esteva I, Alonso M, Costa I, Rial-Rodriguez JM, Rodríguez-Estévez A, Vela A, Castano L, Flück CE. Variants of STAR, AMH and ZFPM2/FOG2 May Contribute towards the Broad Phenotype Observed in 46,XY DSD Patients with Heterozygous Variants of NR5A1. International Journal of Molecular Sciences. 2020; 21(22):8554. https://doi.org/10.3390/ijms21228554

Chicago/Turabian Style

Martínez de LaPiscina, Idoia; Mahmoud, Rana A.; Sauter, Kay-Sara; Esteva, Isabel; Alonso, Milagros; Costa, Ines; Rial-Rodriguez, Jose M.; Rodríguez-Estévez, Amaia; Vela, Amaia; Castano, Luis; Flück, Christa E. 2020. "Variants of STAR, AMH and ZFPM2/FOG2 May Contribute towards the Broad Phenotype Observed in 46,XY DSD Patients with Heterozygous Variants of NR5A1" Int. J. Mol. Sci. 21, no. 22: 8554. https://doi.org/10.3390/ijms21228554

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop