Hereditary spastic paraplegia - childhood onset

Gene: ELOVL1

Amber List (moderate evidence)

ELOVL1 (ELOVL fatty acid elongase 1)
EnsemblGeneIds (GRCh38): ENSG00000066322
EnsemblGeneIds (GRCh37): ENSG00000066322
OMIM: 611813, Gene2Phenotype
ELOVL1 is in 4 panels

2 reviews

Arina Puzriakova (Genomics England Curator)

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

Zornitza Stark (Australian Genomics)

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

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

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
Phenotypes
  • Ichthyotic keratoderma, spasticity, hypomyelination, and dysmorphic facies, OMIM:618527
Tags
missense Q4_21_rating
OMIM
611813
Clinvar variants
Variants in ELOVL1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

23 Nov 2021, Gel status: 2

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: ELOVL1 were updated from 29496980; 32123819; 30487246 to 23689133; 29496980; 30487246; 32123819

23 Nov 2021, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: elovl1 has been classified as Amber List (Moderate Evidence).

23 Nov 2021, Gel status: 0

Added Tag, Added Tag

Arina Puzriakova (Genomics England Curator)

Tag missense tag was added to gene: ELOVL1. Tag Q4_21_rating tag was added to gene: ELOVL1.

23 Nov 2021, Gel status: 0

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

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

19 Sep 2020, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Zornitza Stark (Australian Genomics)

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