title: A novel splice-site mutation in ECM-1 gene in a consanguineous family with lipoid proteinosis.
abstract: 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.
authors.affiliation: Department of Dermatology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Liran
authors.initials: L
authors.lastname: Horev
authors.forename: Tamara
authors.initials: T
authors.lastname: Potikha
authors.forename: Sharon
authors.initials: S
authors.lastname: Ayalon
authors.forename: Vered
authors.initials: V
authors.lastname: Molho-Pessach
authors.forename: Arieh
authors.initials: A
authors.lastname: Ingber
authors.forename: Mohamad Abdel
authors.initials: MA
authors.lastname: Gany
authors.forename: Basel Sad
authors.initials: BS
authors.lastname: Edin
authors.forename: Benjamin
authors.initials: B
authors.lastname: Glaser
authors.forename: Abraham
authors.initials: A
authors.lastname: Zlotogorski
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D003241:Consanguinity; D003596:Cytosine; D004274:DNA, Recombinant; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D006147:Guanine; D006720:Homozygote; D006801:Humans; D007223:Infant; D007438:Introns; D008065:Lipoid Proteinosis of Urbach and Wiethe / Q000235:genetics* / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D012313:RNA
chemical_list: D004274:DNA, Recombinant; C490607:ECM1 protein, human; D016326:Extracellular Matrix Proteins; D006147:Guanine; D012313:RNA; D003596:Cytosine