%0 Case Reports
%T Integration of Phenotype Term Prioritization and Gene Expression Analysis Reveals a Novel Variant in the PERP Gene Associated with Autosomal Recessive Erythrokeratoderma.
%A González-Quintana A
%A Garrido-Moraga R
%A Palencia-Pérez SI
%A Hernández-Martín Á
%A Sánchez-Munárriz J
%A Lezana-Rosales JM
%A Quesada-Espinosa JF
%A Martín MA
%A Arteche-López A
%J Genes (Basel)
%V 14
%N 7
%D 2023 07 22
%M 37510397
%F 4.141
%R 10.3390/genes14071494
%X 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.