Childhood onset hereditary spastic paraplegia
Gene: ELOVL1The rating of this gene has been updated following NHS Genomic Medicine Serviceapproval.Created: 14 Mar 2022, 1:30 p.m. | Last Modified: 14 Mar 2022, 1:30 p.m.
Panel Version: 2.130
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
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 listCreated: 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
Variants in this GENE are reported as part of current diagnostic practice
Tag Q4_21_rating was removed from gene: ELOVL1.
Source Expert Review Green was added to ELOVL1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Publications for gene: ELOVL1 were updated from 29496980; 32123819; 30487246 to 23689133; 29496980; 30487246; 32123819
Gene: elovl1 has been classified as Amber List (Moderate Evidence).
Tag missense tag was added to gene: ELOVL1. Tag Q4_21_rating tag was added to gene: ELOVL1.
Phenotypes for gene: ELOVL1 were changed from Ichthyotic keratoderma, spasticity, hypomyelination, and dysmorphic facies, MIM# 618527 to Ichthyotic keratoderma, spasticity, hypomyelination, and dysmorphic facies, OMIM:618527
gene: ELOVL1 was added gene: ELOVL1 was added to Hereditary spastic paraplegia - childhood onset. Sources: Expert list Mode of inheritance for gene: ELOVL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ELOVL1 were set to 29496980; 32123819; 30487246 Phenotypes for gene: ELOVL1 were set to Ichthyotic keratoderma, spasticity, hypomyelination, and dysmorphic facies, MIM# 618527 Review for gene: ELOVL1 was set to GREEN gene: ELOVL1 was marked as current diagnostic