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A novel splice‐site mutation in ECM‐1 gene in a consanguineous family with lipoid proteinosis
Author(s) -
Horev Liran,
Potikha Tamara,
Ayalon Sharon,
MolhoPessach Vered,
Ingber Arieh,
Gany Mohamad Abdel,
Edin Basel Sad,
Glaser Benjamin,
Zlotogorski Abraham
Publication year - 2005
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.1600-0625.2005.00374.x
Subject(s) - splice site mutation , rna splicing , phenotype , mutation , genetics , intron , splice , exon , exon skipping , gene , biology , extracellular matrix , alternative splicing , loss function , genetic heterogeneity , rna
Lipoid proteinosis (LP) (OMIM 247100) is a rare, autosomal recessive disorder. Recent studies have shown that LP is the result of reduced expression of the extracellular matrix protein gene ( ECM‐1 ), in which loss‐of‐function mutations have been described. In the present report, we describe a large consanguineous family with LP. We identified a homozygous splice‐site mutation in intron 1 (IVS1 + 1G→C) in three clinically affected patients. This is the first splice‐site mutation reported in LP and is the most 5′ of all ECM‐1 mutations described thus far. It is predicted to result in the removal of the translation initiation site, thus ablating all three known ECM‐1 isoforms ( ECM‐1a , ECM‐1b , and ECM‐1c ). In addition, we found a novel splicing variant that is not associated with the disease (DQ010946) and results in the generation of a short, prematurely terminating transcript. This case further emphasizes the role of ECM‐1 in LP and highlights the unresolved genotype–phenotype correlation in this disease.