Allelic heterogeneity of Proteus syndrome.
Cold Spring Harb Mol Case Stud
; 6(3)2020 06.
Article
en En
| MEDLINE
| ID: mdl-32327430
ABSTRACT
Proteus syndrome is a mosaic disorder that can cause progressive postnatal overgrowth of nearly any organ or tissue. To date, Proteus syndrome has been exclusively associated with the mosaic c.49G > A p.(Glu17Lys) pathogenic variant in AKT1, a variant that is also present in many cancers. Here we describe an individual with severe Proteus syndrome who died at 7.5 yr of age from combined parenchymal and restrictive pulmonary disease. Remarkably, this individual was found to harbor a mosaic c.49_50delinsAG p.(Glu17Arg) variant in AKT1 at a variant allele fraction that ranged from <0.01 to 0.46 in fibroblasts established from an overgrown digit. This variant was demonstrated to be constitutively activating by phosphorylation of AKT(S473). These data document allelic heterogeneity for Proteus syndrome. We recommend that individuals with a potential clinical diagnosis of Proteus syndrome who are negative for the p.(Glu17Lys) variant be tested for other variants in AKT1.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Síndrome de Proteo
/
Heterogeneidad Genética
/
Alelos
/
Proteínas Proto-Oncogénicas c-akt
/
Mutación
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Humans
/
Infant
/
Male
Idioma:
En
Revista:
Cold Spring Harb Mol Case Stud
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos