Rare genetic inflammatory skin disorders

Gene: ECM1

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 9 Mar 2022, 2:42 p.m. | Last Modified: 9 Mar 2022, 2:42 p.m.

Panel Version: 1.53

Green List (high evidence)

Comment on list classification: Promoting from grey to amber, with a recommendation for a GREEN rating following GMS review. More than 3 cases reported with a plausible disease causing variant in the ECM1 gene and a Lipoid proteinosis phenotype.

Created: 25 Nov 2021, 5:39 p.m. | Last Modified: 25 Nov 2021, 5:39 p.m.

Panel Version: 1.45

Associated with Urbach-Wiethe disease #247100 (AR) in OMIM.

PMID: 11929856 - Hamada et al 2002 - looked at 6 different unrelated consanguineous families (from Saudi Arabia, Kuwait, Pakistan, The Netherlands, UK, and a group of South African families with a probable common ancestor) with a clinical diagnosis of Lipoid proteinosis (LP)/Urbach–Wiethe disease. They performed a genome-wide linkage analysis and identified a region and then looked at the expression of candidate genes in fibroblasts from patients compared to controls. ECM1 was found to have lower expression levels. 6 homozygous deletion variants were identified in the patients. In one family they established that the parents were heterozygous for the variant.

PMID: 28720532 - Afifi et al 2017 - studied 12 patients from 10 unrelated consanguineous Egyptian families with a clinical diagnosis of lipoid proteinosis. The patients reported progressive hoarseness of voice and easily damaged skin by minor trauma or friction. Homozygous ECM1 variants were detected in affected members in all families: 1 family had a missense variant, 5 families had splice site variants and 4 families had indels predicted to cause frameshifts. Parents were found to be heterozygous for the variants.

PMID: 33159951 - Zhu et al 2021 - a novel homozygous three-nucleotide duplication (c.506_508dupCTG) in ECM in two siblings affected with LP from a consanguineous Chinese family.

Created: 25 Nov 2021, 5:37 p.m. | Last Modified: 25 Nov 2021, 5:37 p.m.

Panel Version: 1.42

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Urbach-Wiethe disease, OMIM:247100; lipoid proteinosis, MONDO:0009530

Publications

• 11929856
• 28720532
• 33159951

Green List (high evidence)

Sources: Other

Created: 21 Oct 2021, 4:26 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Urbach-Wiethe disease

Publications

• 11929856