Lipoid proteinosis: Novel ECM1 pathogenic variants and intrafamilial variability in four unrelated Arab families.

Lipoid proteinosis (LP) is a rare autosomal recessive multisystem disorder that is caused by loss-of-function pathogenic variants in the extracellular matrix protein-1 (ECM1) gene. The typical clinical manifestations of LP include hoarseness of voice, beaded papules on the eyelids, infiltration and scarring of the skin and mucosa, as well as neuropsychological abnormalities. Currently, more than 70 pathogenic variants have been reported, including nonsense, missense, splice site, deletion and insertion pathogenic variants, and more than half of them occurred in exons 6 and 7. Clinical evaluation and Sanger sequencing were performed on eight patients from four unrelated Arab families. We identified two novel ECM1 variants, one nonsense pathogenic variant in exon 6 (c.579G>A, p.Trp193*) and a deletion of three nucleotides (c.1390_1392del, p.Glu464del) in exon 9, and two previously reported frameshift variants; c.692_693delAG, in exon 6 and c.11dupC in exon 1. Although all patients had characteristic manifestations of lipoid proteinosis, we observed intrafamilial phenotypic variability. Our data expand the pathogenic variant spectrum of ECM1 and also supports the fact that exon 6 is one of the most common hot spots of pathological variants in ECM1. © 2022 The Authors. Pediatric Dermatology published by Wiley Periodicals LLC.

Citation

Mingfeng Li, Judith Fischer, Sylvia Safwat, Walaa Shoman, Yasmine El Chazli, Svenja Alter, Cristina Has, Ebtesam Abdalla. Lipoid proteinosis: Novel ECM1 pathogenic variants and intrafamilial variability in four unrelated Arab families. Pediatric dermatology. 2023 Jan;40(1):113-119

Mesh Tags

Substances

PMID: 36670503

search → result