Taken with the previously documented mutations in ECM1, this study supports the view that exons 6 and 7 are the most common sites for ECM1 mutations in lipoid proteinosis.
This study was conducted to investigate the mutation spectrum of ECM1 gene in nine Iranian families having at least one LP patient diagnosed clinically.
Identification of mutation 507delT in a Japanese patient with LiP further supports the thesis that this mutation represents a recurrent mutation in ECM1 in patients with LiP.
Ophthalmological examinations, chart review, ultrasound biomicroscopy, corneal confocal microscopic examinations with Nidek confoScan 4 and direct sequencing of the extracellular matrix protein 1 gene in individuals from three consanguineous Saudi families with LP.
Patients with LP in the present study exhibited point mutations in the ECM1 gene, including one homozygous mutation (C220G) as previously reported, and one novel homozygous mutation c.508insCTG and two heterozygous mutations (C220G/P.R481X and c507delT/c.l473delT).
Together with previously documented mutations in the extracellular matrix protein 1 gene, this study supports the hypothesis that exons 6 and 7 are the most common sites for extracellular matrix protein 1 gene mutations in lipoid proteinosis.
Genetic testing of theECM1 gene showed a homozygous nonsense mutation c.1441C > T (p.Arg481X) in exon 10, confirming the diagnosis of lipoid proteinosis.
Taken with the previously documented mutations in ECM1, this study supports the view that exons 6 and 7 are the most common sites for ECM1 mutations in lipoid proteinosis.
We report the neurologic and neuroradiologic characteristics and ECM1 gene mutations of seven individuals with lipoid proteinosis (LP) from three unrelated consanguineous families.
Missense mutations in the ECM1 gene are an unusual finding in lipoid proteinosis, but this case adds to the spectrum of disease-associated mutations in this rare genodermatosis.
We reported previously that unlike the BRICHOS misfolding SFTPC mutants, expression of hSP-C(I73T) induces lung remodeling and alveolar lipoproteinosis without a substantial Endoplasmic Reticulum (ER) stress response or ER-mediated intrinsic apoptosis.
The absence of functional domains and truncated sequence most likely contribute to the lack of ECM1 function and thereby influence several aspects of dermal homeostasis that leads to LP pathogenesis.