Integration of Phenotype Term Prioritization and Gene Expression Analysis Reveals a Novel Variant in the PERP Gene Associated with Autosomal Recessive Erythrokeratoderma.
Genes (Basel)
; 14(7)2023 07 22.
Article
en En
| MEDLINE
| ID: mdl-37510397
ABSTRACT
Hereditary palmoplantar keratodermas (PPKs) are a clinically and genetically heterogeneous group of disorders characterized by excessive epidermal thickening of palms and soles. Several genes have been associated with PPK including PERP, a gene encoding a crucial component of desmosomes that has been associated with dominant and recessive keratoderma. We report a patient with recessive erythrokeratoderma (EK) in which whole exome sequencing (WES) prioritized by human phenotype ontology (HPO) terms revealed the presence of the novel variant c.153C > A in the N-terminal region the PERP gene. This variant is predicted to have a nonsense effect, p.(Cys51Ter), resulting in a premature stop codon. We demonstrated a marked reduction in gene expression in cultured skin fibroblasts obtained from the patient. Despite the PERP gene is expressed at low levels in fibroblasts, our finding supports a loss-of-function (LoF) mechanism for the identified variant, as previously suggested in recessive EK. Our study underscores the importance of integrating HPO analysis when using WES for molecular genetic diagnosis in a clinical setting, as it facilitates continuous updates regarding gene-clinical feature associations.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Queratodermia Palmoplantar
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Genes (Basel)
Año:
2023
Tipo del documento:
Article
País de afiliación:
España
Pais de publicación:
CH
/
SUIZA
/
SUÍÇA
/
SWITZERLAND