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Title: A 46,XX testicular disorder of sex development caused by a Wilms' tumour Factor-1 (WT1) pathogenic variant
Authors: GOMES, Nathalia L.PAULA, Leila C. P. deSILVA, Juliana M.SILVA, Thatiana E.LERARIO, Antonio M.NISHI, Mirian Y.BATISTA, Rafael L.FARIA JUNIOR, Jose A. D.MORAES, DanielaCOSTA, Elaine M. F.HEMESATH, Tatiana P.GUARAGNA-FILHO, GuilhermeLEITE, Julio C. L.CARVALHO, Clarissa G.DOMENICE, SorahiaCOSTA, Eduardo C.MENDONCA, Berenice B.
Citation: CLINICAL GENETICS, v.95, n.1, p.172-176, 2019
Abstract: 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.
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Artigos e Materiais de Revistas Científicas - FM/MCM
Departamento de Clínica Médica - FM/MCM

Artigos e Materiais de Revistas Científicas - HC/ICESP
Instituto do Câncer do Estado de São Paulo - HC/ICESP

Artigos e Materiais de Revistas Científicas - HC/ICHC
Instituto Central - HC/ICHC

Artigos e Materiais de Revistas Científicas - HC/IPq
Instituto de Psiquiatria - HC/IPq

Artigos e Materiais de Revistas Científicas - LIM/42
LIM/42 - Laboratório de Hormônios e Genética Molecular

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