Molecular analysis of lipoid proteinosis: identification of a novel nonsense mutation in the ECM1 gene in a Pakistani family

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.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.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.Lipoid proteinosis (LP; MIM 247100) also known as Urbach-Wiethe disease or hyalinosis cutis et mucosae, was first reported by Urbach and Wiethe, in 1929 [1]. It is a rare genetic disease, which is inherited in an autosomal recessive fashion. The disease occurs worldwide but is more common in certain geographical areas such as the Northern Cape province of South Africa, including Namaqualand. Clinical heterogeneity is reported in LP [2], although it usually presents in early childhood with hoarseness, caused by infiltration of the laryngeal mucosa [3]. Skin lesions or pox-like scars usually appear simultaneously or shortly afterwards. Other characteristic findings include the arrangement of 'beaded' waxy papules, known as moniliform blepharosis, which may be present along the margins of both eyelids [4,5]. Histological and ultra structural examination has revealed the widespread deposition of hyaline-like material and disruption/reduplication of basement membrane around blood vessels and at the dermal-epidermal junction, mouth and upper respiratory tract, and other internal organs [2,6]. Overproduction of normally expressed non-collagenous protein in the hyaline material has also been reported [7]. Tongue is oft