Extraskeletal chondroma of the toe in a child with DICER1 tumor predisposition syndrome: support for a dominant negative mechanism.
Virchows Arch
; 484(6): 1023-1027, 2024 Jun.
Article
en En
| MEDLINE
| ID: mdl-38355738
ABSTRACT
DICER1 tumor predisposition syndrome is a pleiotropic disorder that gives rise to various mainly pediatric-onset lesions. We report an extraskeletal chondroma (EC) of the great toe occurring in a child who, unusually, carries a germline "hotspot" missense DICER1 variant rather than the more usual loss-of-function (LOF) variant. No heterozygous LOF allele was identified in the EC. We demonstrate this variant impairs 5p cleavage of precursor-miRNA (pre-miRNA) and competes with wild-type (WT) DICER1 protein for pre-miRNA processing. These results suggest a mechanism through which a germline RNase IIIb variant could impair pre-miRNA processing without complete LOF of the WT DICER1 allele.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Condroma
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Predisposición Genética a la Enfermedad
/
Ribonucleasa III
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ARN Helicasas DEAD-box
Límite:
Child
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Female
/
Humans
/
Male
Idioma:
En
Revista:
Virchows Arch
Asunto de la revista:
BIOLOGIA MOLECULAR
/
PATOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Canadá