A 46,XX testicular disorder of sex development caused by a Wilms' tumour Factor-1 (WT1) pathogenic variant
| Autor: | Berenice B. Mendonca, Leila Cristina Pedroso de Paula, Júlio César Loguercio Leite, Eduardo Castro da Costa, Thatiana Evilen da Silva, Daniela A. Moraes, Guilherme Guaragna-Filho, Sorahia Domenice, Clarissa Gutierrez Carvalho, Jose Antonio Diniz Faria Junior, Nathalia Lisboa Gomes, Tatiana Prade Hemesath, Mirian Yumie Nishi, Elaine Maria Frade Costa, Juliana M Silva, Antonio M. Lerario, Rafael Loch Batista |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male congenital hereditary and neonatal diseases and abnormalities Heterozygote 46 XX Disorders of Sex Development Testicular Disorder Population Gonadal dysgenesis 030105 genetics & heredity Biology urologic and male genital diseases Testicular Diseases Frameshift mutation 03 medical and health sciences Testis Genetics medicine Humans Disorders of sex development Pathology Molecular education Child WT1 Proteins Genetics (clinical) Zinc finger education.field_of_study Massive parallel sequencing urogenital system Sexual Development Infant medicine.disease Phenotype female genital diseases and pregnancy complications DNA-Binding Proteins 030104 developmental biology Mutation Female |
| Zdroj: | Clinical genetics. 95(1) |
| ISSN: | 1399-0004 |
| Popis: | Molecular diagnosis is rarely established in 46,XX testicular (T) disorder of sex development (DSD) individuals with atypical genitalia. The Wilms' tumour factor-1 (WT1) gene is involved in early gonadal development in both sexes. Classically, WT1 deleterious variants are associated with 46,XY disorders of sex development (DSD) because of gonadal dysgenesis. We report a novel frameshift WT1 variant identified in an SRY-negative 46,XX testicular DSD girl born with atypical genitalia. Target massively parallel sequencing involving DSD-related genes identified a novel heterozygous WT1 c.1453_1456del; p.Arg485Glyfs*14 variant located in the fourth zinc finger of the protein which is absent in the population databases. Segregation analysis and microsatellite analysis confirmed the de novo status of the variant that is predicted to be deleterious by in silico tools and to increase WT1 target activation in crystallographic model. This novel and predicted activating frameshift WT1 variant leading to the 46,XX testicular DSD phenotype includes the fourth zinc-finger DNA-binding domain defects in the genetic aetiology of 46,XX DSD. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text