Variants of STAR, AMH and ZFPM2/FOG2 May Contribute towards the Broad Phenotype Observed in 46,XY DSD Patients with Heterozygous Variants of NR5A1
| Autor: | Amaia Rodríguez-Estévez, Luis Castaño, Amaia Vela, Milagros Alonso, Idoia Martínez de LaPiscina, Christa E. Flück, Jose Manuel Rial-Rodriguez, Ines Costa, Isabel Esteva, Rana Aa Mahmoud, Kay-Sara Sauter |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Steroidogenic factor 1 Male Multifactorial Inheritance DSD NR5A1/SF1 lcsh:Chemistry Transactivation disorder/difference of sex development difference of sex development 0302 clinical medicine Sex hormone-binding globulin AMH nuclear receptor Disorders of sex development Child 610 Medicine & health lcsh:QH301-705.5 Spectroscopy Genetics biology STAR Inheritance (genetic algorithm) General Medicine genotype–phenotype correlation disorder Phenotype FOG2 Computer Science Applications genotype– DNA-Binding Proteins SF1 Child Preschool SF-1 Female adrenal insufficiency transcription Heterozygote endocrine system Adolescent Receptors Peptide 030209 endocrinology & metabolism Catalysis Article Inorganic Chemistry 03 medical and health sciences medicine Humans In patient Physical and Theoretical Chemistry gene Molecular Biology Gene Disorder of Sex Development 46 XY sex development Organic Chemistry Infant Newborn Genetic Variation Infant steroidogenic factor 1 medicine.disease Phosphoproteins mutations 030104 developmental biology lcsh:Biology (General) lcsh:QD1-999 phenotype correlation binding domain biology.protein oligogenic disorders 570 Life sciences Receptors Transforming Growth Factor beta Transcription Factors |
| Zdroj: | Martínez de LaPiscina, Idoia; Mahmoud, Rana Aa; Sauter, Kay-Sara; Esteva, Isabel; Alonso, Milagros; Costa, Ines; Rial-Rodriguez, Jose Manuel; 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. International journal of molecular sciences, 21(22) MDPI 10.3390/ijms21228554 Addi. Archivo Digital para la Docencia y la Investigación instname International Journal of Molecular Sciences, Vol 21, Iss 8554, p 8554 (2020) Addi: Archivo Digital para la Docencia y la Investigación Universidad del País Vasco International Journal of Molecular Sciences Volume 21 Issue 22 |
| Popis: | 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. This research was funded in part by a grant from the Basque Department of Education (IT795-13) and a personal research fellowship grant from the Spanish Pediatric Endocrine Society to IM. Several authors (IM, LC) of this work are members of the European Reference Network for Endo-ERN (Project ID No 739527). RM is supported by a personal research fellowship grant of Science by Women from the Women for Africa foundation. |
| Databáze: | OpenAIRE |
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