Identification of a novel three-nucleotide duplication in ECM1 in Chinese siblings affected with lipoid proteinosis.

Lipoid proteinosis (LP) is a rare autosomal recessive disorder caused by pathological mutations in the glycoprotein extracellular matrix protein 1 gene (ECM1). In this study, we examined two sibling patients who were suspected of LP in a consanguineous Chinese family for clinical manifestations and sequenced the all coding exonic regions of ECM1 in the proband. Both siblings were detected a homozygous three-nucleotide duplication, c.506_508dupCTG in the exon 6 of ECM1. This mutation introduces an alanine addition between two highly conserved amino acids (Pro169 and Gly170), designated as p.169_170insA, within one of the two tandem repeat domains which are functional important for protein-protein interactions. Their parents were unaffected and heterozygous for this mutation. This mutation wasn't found in one hundred normal Chinese individuals screened and wasn't previously reported elsewhere, excluding it as a common neutral polymorphism. These evidences supported this duplication as the causative mutation of LP. Our finding expanded the spectrum of disease-causing mutations in LP and provides further evidence for the importance of ECM1 gene in the development of this rare genodermatosis.