title: Molecular analysis of lipoid proteinosis: identification of a novel nonsense mutation in the ECM1 gene in a Pakistani family.
abstract: Lipoid proteinosis is a rare autosomal recessive disease characterized by cutaneous and mucosal lesions and hoarseness appearing in early childhood that is caused by homozygous or compound heterozygous mutations in the ECM1 gene located on chromosome 1q21. The aim of the study was to investigate the molecular genetic defect underlying lipoid proteinosis in a consanguineous Pakistani family.
  
  
  METHODS
  Genotyping of seven members of the family was performed by amplifying microsatellite markers, tightly linked to the ECM1 gene. To screen for mutations in the ECM1 gene, all of its exons and splice junctions were PCR amplified from genomic DNA and analyzed by SSCP and sequenced directly in an ABI 3130 genetic analyzer.
  
  
  RESULTS
  The results revealed linkage of the LP family to the ECM1 locus. Sequence analysis of the coding exons and splice junctions of the ECM1 gene revealed a novel homozygous mutation (c.616C > T) in exon 6, predicted to replace glutamine with stop codon (p.Q206X) at amino acid position 206.
  
  
  CONCLUSIONS
  The finding of a novel mutation in Pakistani family extends the body of evidence that supports the importance of ECM1 gene for the development of lipoid proteinosis.
authors.affiliation: Institute of Biomedical and Genetic Engineering, GPO Box 2891, 24-Mauve Area, G-9⁄1, Islamabad, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Nasir
authors.forename: Amir
authors.initials: A
authors.lastname: Latif
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ajmal
authors.forename: Reem
authors.initials: R
authors.lastname: Qamar
authors.forename: Muhammad
authors.initials: M
authors.lastname: Naeem
authors.forename: Abdul
authors.initials: A
authors.lastname: Hameed
mesh_terms: D000293:Adolescent; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005091:Exons; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D008065:Lipoid Proteinosis of Urbach and Wiethe / Q000235:genetics*; D018895:Microsatellite Repeats; D010154:Pakistan; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D022821:RNA Splice Sites; D012867:Skin / Q000473:pathology; D055815:Young Adult
chemical_list: D018389:Codon, Nonsense; C490607:ECM1 protein, human; D016326:Extracellular Matrix Proteins; D022821:RNA Splice Sites