Hereditary neuropathy or pain disorder

Gene: EMILIN1

Green List (high evidence)

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

Created: 24 Feb 2025, 5:02 p.m. | Last Modified: 24 Feb 2025, 5:02 p.m.

Panel Version: 6.148

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Comment on list classification: This is now sufficient evidence to promote this gene to Green at the next GMS panel update. At least three unrelated families reported with heterozygous variant in the EMILIN1 gene and neuropathy.

The third family (PMID:38963291) includes a proband with childhood-onset sensory-motor neuropathy and pyramidal signs (ataxic-spastic gait). Sequencing revealed two heterozygous missense variants, c.544G>A and c.546G>C, which authors renamed as c.544_546GAG>AAC (p.E182N) as the variants were in cis and located at the same protein residue. The proband's mother, carrying the same variant, presented with a milder peripheral nerve disorder, hypermobility of joints and ligamentous laxity, and moderate inflammatory arthropathy.

Created: 23 Oct 2024, 2:27 p.m. | Last Modified: 23 Oct 2024, 2:27 p.m.

Panel Version: 5.66

Green List (high evidence)

3rd case now reported 0 reference attached so should now be green

Created: 20 Oct 2024, 9:41 a.m. | Last Modified: 20 Oct 2024, 9:41 a.m.

Panel Version: 5.19

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
peripheral neuropathy

Publications

• 38963291

I don't know

Comment on list classification: As reviewed by Zornitza Stark, there are two unrelated families in support of the association of monoallelic EMILIN1 variants with peripheral neuropathy and hence this gene should be rated amber with current evidence.

Created: 6 Jan 2024, midnight | Last Modified: 6 Jan 2024, midnight

Panel Version: 3.71

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Neuronopathy, distal hereditary motor, autosomal dominant 10, OMIM:620080

I don't know

Missense mutations identified in two families. First family, proband presented with ascending and descending aortic aneurysms, bilateral lower leg and foot sensorimotor peripheral neuropathy, arthropathy, and increased skin elasticity. Variant segregated with disease in the affected proband, mother, and son. Second family, father and three affected children showed amyotrophy and weakness of the distal lower limbs, dating back to early childhood. Some functional studies performed in patient fibroblasts and zebrafish, however these were not conclusive as the two missense mutations are at different locations within the protein.
Sources: Literature

Created: 1 Jul 2020, 10:12 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Peripheral neuropathy; aortic aneurysm

Publications

• 31978608
• 26462740