A Rare Homozygous Synonymous Variant in the ECM1 Gene in a Lipoid Proteinosis Patient.

Abstract

Lipoid proteinosis (LP) is a rare autosomal recessive disorder resulting from mutations in the ECM1 gene and characterized by mucocutaneous thickening and deposition of hyaline material. We present a 10-year-old male with hoarseness, moniliform blepharosis, oral mucosal nodules, and cutaneous lesions. Histopathology showed PAS-positive hyaline material deposition. Genetic analysis by next-generation sequencing identified a homozygous synonymous variation, ECM1 c.879G>A (p.Ser293=), which has not been previously reported in a homozygous form. Segregation analysis showed heterozygosity in both parents. In accordance with ACMG guidelines, the variant meets criteria PS4, PM2, PM3, PP3, and PP4, supporting its reclassification as pathogenic. This case highlights the diagnostic value of combining clinical, histological, and genomic data, especially in the evaluation of variations of uncertain significance. Genotyping in patients clinically and histopathologically compatible with LP is crucial to inform disease management and enhance understanding of its genetic background.