Whole exome sequencing identified a rare WT1 loss-of-function variant in a non-syndromic POI patient.
Mol Genet Genomic Med
; 10(1): e1820, 2022 01.
Article
em En
| MEDLINE
| ID: mdl-34845858
ABSTRACT
BACKGROUND:
Premature ovarian insufficiency (POI) is a highly heterogeneous disease, and up to 25% of cases can be explained by genetic causes. The transcription factor WT1 has long been reported to play a crucial role in ovary function. Wt1-mutated female mice exhibited POI-like phenotypes. METHODS ANDRESULTS:
In this study, whole exome sequencing (WES) was applied to find the cause of POI in Han Chinese women. A nonsense variant in the WT1 gene NM_024426.6c.1387C>T(p.R463*) was identified in a non-syndromic POI woman. The variant is a heterozygous de novo mutation that is very rare in the human population. The son of the patient inherited the mutation and developed Wilms' tumor and urethral malformation at the age of 7. According to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) guidelines, the novel variant is categorized as pathogenic. Western blot analysis further demonstrated that the WT1 variant could produce a truncated WT1 isoform in vitro.CONCLUSIONS:
A rare heterozygous nonsense WT1 mutant is associated with non-syndromic POI and Wilms' tumor. Our finding characterized another pathogenic WT1 variant, providing insight into genetic counseling.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Menopausa Precoce
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Insuficiência Ovariana Primária
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Tumor de Wilms
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
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Male
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article