Striate palmoplantar keratoderma: a novel DSG1 mutation, combined with an LDLR mutation.

Background: Palmoplantar keratoderma (PPK) is a heterogeneous group of disorders characterized by abnormal thickening of the skin on the palms and soles. Striate palmoplantar keratoderma (SPPK) is commonly caused by heterozygous mutations in the desmoglein-1 (DSG1) gene.

Objective: This study aimed to report a case of a 36-year-old Chinese female patient with SPPK caused by a novel DSG1 gene mutation, along with her family history, and explore its potential relationship with other genetic variants.

Methods: Whole-exome sequencing was performed on the patient and their family members to identify the pathogenic mutation, which was validated by Sanger sequencing. Histological and electron microscopy analyses were conducted to examine the pathological characteristics of skin tissue.of skin tissue.

Results: A frameshift mutation, c.1285del, in exon 10 of the DSG1 gene was identified, leading to a loss of protein function and resulting in SPPK. This mutation was also detected in two other family members with similar phenotypes. Additionally, a classical splicing variant, c.313+2dup, in the low-density lipoprotein receptor (LDLR) gene associated with hypercholesterolemia was identified in the patient; however, no direct association with SPPK was observed.

Conclusion: This study was the first to report a novel mutation in the DSG1 gene associated with SPPK and suggested a potential role of the LDLR gene variant in SPPK patients, providing new insights for further research into the genetic mechanisms underlying SPPK.