An unusual presentation of Denys-Drash syndrome due to bigenic disease.
Pediatrics
; 133(1): e252-6, 2014 Jan.
Article
em En
| MEDLINE
| ID: mdl-24379226
ABSTRACT
We report a case of Denys-Drash syndrome (DDS) in a 3-month-old girl presenting with bilateral renal cortical cysts mimicking polycystic kidney disease. Genetic analysis revealed a de novo heterozygous missense mutation c.1186G>A (p.Asp396Asn) in the WT1 gene, confirming the diagnosis of DDS. Because multiple renal cysts have never been reported in DDS, we explored several genes responsible for these renal manifestations, such as HNF-1ß, PAX2, PKD1, and PKD2. Remarkably, we identified a heterozygous missense variant c.12439A>G (p.Lys4147Glu) in the PKD1 gene. The same variant was found in the patient's mother, who had no renal cysts, and in the grandfather, who had several renal cysts. Mutation prediction programs classified the c.12439A>G variant as being "likely pathogenic." We hypothesize that the severe cystic phenotype in the index patient could be due to the WT1 mutation, enhancing pathogenicity of the "hypomorph" PKD1 allele. A possible role for Wilms tumor suppressor 1 (WT1) in renal cyst development should be considered. From a conceptual point of view, this case shows that an unusual presentation of a known genetic syndrome might point to bigenic inheritance, with unexpected interference of mutated genes causing an uncommon clinical phenotype.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Genes do Tumor de Wilms
/
Rim Policístico Autossômico Dominante
/
Mutação de Sentido Incorreto
/
Síndrome de Denys-Drash
/
Canais de Cátion TRPP
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Female
/
Humans
/
Infant
Idioma:
En
Revista:
Pediatrics
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Bélgica