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Integration of Phenotype Term Prioritization and Gene Expression Analysis Reveals a Novel Variant in the PERP Gene Associated with Autosomal Recessive Erythrokeratoderma.
- Source :
- Genes; Jul2023, Vol. 14 Issue 7, p1494, 8p
- Publication Year :
- 2023
-
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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 20734425
- Volume :
- 14
- Issue :
- 7
- Database :
- Complementary Index
- Journal :
- Genes
- Publication Type :
- Academic Journal
- Accession number :
- 169326047
- Full Text :
- https://doi.org/10.3390/genes14071494