White matter disorders and cerebral calcification - narrow panel

Gene: ELOVL1

Green List (high evidence)

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

Created: 30 Jan 2023, 4:26 p.m. | Last Modified: 30 Jan 2023, 4:26 p.m.

Panel Version: 2.9

Green List (high evidence)

Comment on list classification: New gene added by Zornitza Stark. Although only a single variant has been reported to date this was shown to arise de novo in unrelated individuals and the possibility of a founder effect was ruled out. Pathogenicity is supported by functional data including in vitro studies of the variant and complimentary animal models. Overall this is sufficient evidence to rate this gene as Green at the next GMS panel update.

Created: 23 Nov 2021, 11:19 a.m. | Last Modified: 23 Nov 2021, 11:19 a.m.

Panel Version: 2.106

Single heterozygous ELOVL1 variant (c.494C>T, p.S165F) identified in two boys of Polish ancestry; however, haplotype analysis revealed that the variant was not derived from a founder allele. Clinical presentation in both individuals was homogenous and included ichthyosis, hypomyelination, spastic paraplegia and optic atrophy. Elovl1 mutant mice display similar phenotypes including deficits in motor coordination, hypomyelination and skin alterations.

Created: 23 Nov 2021, 11:15 a.m. | Last Modified: 23 Nov 2021, 11:15 a.m.

Panel Version: 2.105

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Ichthyotic keratoderma, spasticity, hypomyelination, and dysmorphic facies, OMIM:618527

Publications

• 23689133
• 29496980
• 30487246
• 32123819

Green List (high evidence)

Ichthyotic keratoderma, spasticity, hypomyelination, and dysmorphic features (IKSHD) is characterized by epidermal hyperproliferation and increased keratinization, resulting in ichthyosis; hypomyelination of central white matter, causing spastic paraplegia and central nystagmus; and optic atrophy, resulting in reduction of peripheral vision and visual acuity. Affected individuals have mild facial dysmorphism.

Same two individuals reported in two publications. Both had the same variant, p.S165F, which arose de novo, suggesting the residue is important in pathogenesis. Mouse model.
Sources: Expert list

Created: 19 Sep 2020, 7:16 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Ichthyotic keratoderma, spasticity, hypomyelination, and dysmorphic facies, MIM# 618527

Publications

• 29496980
• 32123819
• 30487246

Variants in this GENE are reported as part of current diagnostic practice