HGNC Approved Gene Symbol: ECM1
SNOMEDCT: 38692000;
Cytogenetic location: 1q21.2 Genomic coordinates (GRCh38): 1:150,508,109-150,513,789 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 1q21.2 | Urbach-Wiethe disease | 247100 | Autosomal recessive | 3 |
Mathieu et al. (1994) identified a novel 85-kD protein secreted by a mouse osteogenic stromal cell line. Bhalerao et al. (1995) showed that the full-length cDNA is 1.9 kb and contains an open reading frame of 1,677 bp that codes for a protein of 559 amino acids.
Smits et al. (1997) described a genomic clone containing the human homolog, termed extracellular matrix protein 1 (ECM1), from a chromosome 1 cosmid library. The ECM1 gene appeared to be expressed as a 1.8-kb transcript predominantly in placenta and heart, while an additional 1.4-kb alternatively spliced message was detected in tonsils. The full-length human ECM1 transcript contains 1,838 bp and has an overall homology of 79.6% with the mouse Ecm1 cDNA. The transcript codes for a protein of 540 amino acids that is 69.4% identical and 81.3% similar to the corresponding mouse protein. The alternatively spliced variant, 1,450 bp long, encodes a protein of 415 amino acids.
Smits et al. (1997) demonstrated that the coding region of the human ECM1 gene comprises 10 exons.
Oyama et al. (2003) noted that HLA-subtype susceptibility and high rates of other autoimmune disorders suggest that autoantibodies to specific mucocutaneous antigens may be involved in the etiology of lichen sclerosis (151590). The clinicopathologic similarities between lichen sclerosis and lipoid proteinosis, which results from mutations in ECM1, suggested that this protein may be an autoantigen in lichen sclerosis. By immunoblotting, IgG autoantibodies to ECM1 were found in 20 of 30 lichen sclerosis serum samples. The highest titer was 1 in 20. These samples, and those from 56 other patients with lichen sclerosis, showed immunoreactivity to the recombinant ECM1 protein; 6 of 85 control serum samples were positive. The findings suggested that specific humeral immune response to ECM1 may be involved in the etiology of lichen sclerosis and may offer help in disease diagnosis, monitoring, and approaches to treatment.
By fluorescence in situ hybridization, Smits et al. (1997) mapped the ECM1 gene to 1q21 outside the epidermal differentiation complex region (see 152445). Bhalerao et al. (1995) mapped the gene to mouse chromosome 3.
Lipoid proteinosis, also known as hyalinosis cutis et mucosae or Urbach-Wiethe disease (247100), is a rare, autosomal recessive disorder typified by generalized thickening of skin, mucosae, and certain viscera. Classic features include beaded eyelid papules and laryngeal infiltration leading to hoarseness. Histologically, there is widespread deposition of hyaline (glycoprotein) material and disruption/reduplication of basement membrane. Using DNA from 6 consanguineous families, Hamada et al. (2002) mapped the disorder to chromosome 1q21 at marker D1S498 (lod = 21.85 at theta = 0), within a 2.3-cM critical region. Using a candidate gene approach, the authors identified 6 different homozygous loss-of-function mutations in ECM1.
In affected individuals of a consanguineous Kuwaiti family with lipoid proteinosis (247100), Hamada et al. (2002) identified homozygosity for a single-basepair deletion (A1019) in exon 7 of the ECM1 gene. The mutation resulted in a premature stop codon 108 bp downstream.
Hamada et al. (2002) identified a 14-year old Pakistani boy with lipoid proteinosis (247100); he was the product of a consanguineous mating, and was homozygous for a C-to-T transition at position 1036 in exon 7 of the ECM1 gene. The mutation resulted in conversion of codon gln346 to a premature stop codon (Q346X).
Hamada et al. (2002) reported 4 sibs affected with lipoid proteinosis (247100) within a consanguineous Saudi family. All affected individuals were homozygous for an 1163-bp deletion in the ECM1 gene, which eliminated part of intron 8 and all of exons 9 and 10.
In 2 unrelated subjects with lipoid proteinosis (247100) with different ECM1 haplotypes, Hamada et al. (2003) identified a 507delT mutation in exon 6 of the ECM1 gene. The authors suggested that the deletion, which causes a frameshift and premature termination 23 bp downstream, may represent a recurrent mutation in lipoid proteinosis.
In a patient with lipoid proteinosis (247100), Hamada et al. (2003) identified a homozygous arg53-to-ter (R53X) mutation in exon 3 of the ECM1 gene.
In a 2 year-old boy with lipoid proteinosis (247100) from a nonconsanguineous family, Hamada et al. (2003) identified a heterozygous phe167-to-ile (F167I) mutation in exon 6 of the ECM1 gene. He carried a trp160-to-ter (W160X) mutation, also in exon 6, on the other allele.
See 602201.0006 and Hamada et al. (2003).
Bhalerao, J., Tylzanowski, P., Filie, J. D., Kozak, C. A., Merregaert, J. Molecular cloning, characterization, and genetic mapping of the cDNA coding for a novel secretory protein of the mouse: demonstration of alternative splicing in skin and cartilage. J. Biol. Chem. 270: 16385-16394, 1995. [PubMed: 7608209] [Full Text: https://doi.org/10.1074/jbc.270.27.16385]
Hamada, T., McLean, W. H. I., Ramsay, M., Ashton, G. H. S., Nanda, A., Jenkins, T., Edelstein, I., South, A. P., Bleck, O., Wessagowit, V., Mallipeddi, R., Orchard, G. E., and 12 others. Lipoid proteinosis maps to 1q21 and is caused by mutations in the extracellular matrix protein 1 gene (ECM1). Hum. Molec. Genet. 11: 833-840, 2002. [PubMed: 11929856] [Full Text: https://doi.org/10.1093/hmg/11.7.833]
Hamada, T., Wessagowit, V., South, A. P., Ashton, G. H. S., Chan, I., Oyama, N., Siriwattana, A., Jewhasuchin, P., Charuwichitratana, S., Thappa, D. M., Jeevankumar, B., Lenane, P., Krafchik, B., and 9 others. Extracellular matrix protein 1 gene (ECM1) mutations in lipoid proteinosis and genotype-phenotype correlation. J. Invest. Derm. 120: 345-350, 2003. Note: Erratum: J. Invest. Derm. 123: 805-806, 2004. [PubMed: 12603844] [Full Text: https://doi.org/10.1046/j.1523-1747.2003.12073.x]
Mathieu, E., Meheus, L., Raymackers, J., Merregaert, J. Characterization of the osteogenic stromal cell line MN7: identification of secreted MN7 proteins using two-dimensional polyacrylamide gel electrophoresis, western blotting, and microsequencing. J. Bone Miner. Res. 9: 903-913, 1994. [PubMed: 8079665] [Full Text: https://doi.org/10.1002/jbmr.5650090616]
Oyama, N., Chan, I., Neill, S. M., Hamada, T., South, A. P., Wessagowit, V., Wojnarowska, F., D'Cruz, D., Hughes, G. J., Black, M. M., McGrath, J. A. Autoantibodies to extracellular matrix protein 1 in lichen sclerosis. Lancet 362: 118-123, 2003. [PubMed: 12867112] [Full Text: https://doi.org/10.1016/S0140-6736(03)13863-9]
Smits, P., Ni, J., Feng, P., Wauters, J., Van Hul, W., El Boutaibi, M., Dillon, P. J., Merregaert, J. The human extracellular matrix gene 1 (ECM1): genomic structure, cDNA cloning, expression pattern, and chromosomal localization. Genomics 45: 487-495, 1997. [PubMed: 9367673] [Full Text: https://doi.org/10.1006/geno.1997.4918]