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Case Reports
. 2010 Dec 31;4(4):66-70.
doi: 10.3315/jdcr.2010.1056.

Homozygous frame shift mutation in ECM1 gene in two siblings with lipoid proteinosis

Azam J Samdani  1 , Abid Azhar, Syed M Shahid, Syeda N Nawab, Rozeena Shaikh, Shah A Qader, Qaisar Mansoor, Bahram K Khoso, Muhammad Ismail
Affiliations
Case Reports

Homozygous frame shift mutation in ECM1 gene in two siblings with lipoid proteinosis

Azam J Samdani et al. J Dermatol Case Rep. .

Abstract

Background: The extracellular matrix protein 1 (ECM1) is a glycoprotein, expressed in skin and other tissues. Loss-of-function mutation in ECM1 causes a rare autosomal recessive disorder called lipoid proteinosis. Lipoid proteinosis is presented by varying degrees of skin scars, beaded papules along the eyelid margins, variable signs of hoarseness of voice and respiratory disorders. More than 250 cases of this disorder have been described in the literature, but occurrence of lipoid proteinosis in siblings is very rare. This study was designed to investigate the possible mutation causing lipoid proteinosis in a Pakistani family and to elaborate the scope of possible genetic changes, causing the genodermatosis in Pakistan.

Main observations: In this study, two siblings (12 and 9-years sisters) were presented with scaly itchy lesions on whole body, hoarse voice and macroglossia. Their deceased father had similar clinical manifestations but mother and younger brother were unaffected. Blood samples from clinically affected and unaffected family members were collected with informed consent. The coding region of ECM1 gene containing 10 exons were amplified and sequenced. Both the affected siblings were shown to have homozygous frame shift mutation by deletion of the nucleotide T at 507, codon 169, exon 6. This resulted in a frame shift from codon 169 and appearance of a premature stop codon at 177, causing formation of a mutated protein (176 amino acids) instead of normal ECM1 protein (540 amino acids).

Conclusion: A case of homozygous 62-bp insertion in ECM1 gene causing lipoid proteinosis has been reported in another Pakistani family. The current study presents a homozygous frame shift mutation supporting an unusual function of ECM1 protein and broadens the spectrum of disease-linked mutations in this rare case of genodermatosis in this region.

Keywords: ECM1; extracellular matrix protein 1; gene; genodermatosis; lipoid proteinosis; mutation.

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Figures

Figure 1
Figure 1
Lipoid proteinosis. Warty skin on the dorsal aspect of hands in both siblings (A), acneiform scars on the back (B), fleshcolored beaded papules on the edges of eyelids (C) and oral mucosa with yellow-white infiltrates.
Figure 2
Figure 2
Pedigree of the family studied shows that both the parents are heterozygous carrier. Two sisters are homozygous patients and the only brother is unaffected (carrier).
Figure 3
Figure 3
Direct sequencing of PCR products amplified from exon 6 of ECM1 gene. The patients show a homozygous mutation of c.507delT (red arrow) as compared to Carrier without deletion (green arrow).
Figure 4
Figure 4
Complete ECM1 gene (normal and mutated) showing premature termination at 177.
See this image and copyright information in PMC

References

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