Lipoid proteinosis: Novel ECM1 pathogenic variants and intrafamilial variability in four unrelated Arab families.
ECM1
extracellular matrix protein 1
lipoid proteinosis
pathogenic variant
Journal
Pediatric dermatology
ISSN: 1525-1470
Titre abrégé: Pediatr Dermatol
Pays: United States
ID NLM: 8406799
Informations de publication
Date de publication:
Jan 2023
Jan 2023
Historique:
received:
10
04
2022
accepted:
23
07
2022
entrez:
20
1
2023
pubmed:
21
1
2023
medline:
25
1
2023
Statut:
ppublish
Résumé
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.
Sections du résumé
BACKGROUND/OBJECTIVES
OBJECTIVE
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.
METHODS
METHODS
Clinical evaluation and Sanger sequencing were performed on eight patients from four unrelated Arab families.
RESULTS
RESULTS
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.
CONCLUSIONS
CONCLUSIONS
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.
Substances chimiques
Extracellular Matrix Proteins
0
ECM1 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
113-119Subventions
Organisme : China Scholarship Council
Informations de copyright
© 2022 The Authors. Pediatric Dermatology published by Wiley Periodicals LLC.
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