Hereditary spastic paraplegia - childhood onset

Gene: HIKESHI

Amber List (moderate evidence)

HIKESHI (Hikeshi, heat shock protein nuclear import factor)
EnsemblGeneIds (GRCh38): ENSG00000149196
EnsemblGeneIds (GRCh37): ENSG00000149196
OMIM: 614908, Gene2Phenotype
HIKESHI is in 5 panels

2 reviews

Ivone Leong (Genomics England Curator)

Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM but not in Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Created: 26 May 2021, 3:16 p.m. | Last Modified: 26 May 2021, 3:16 p.m.
Panel Version: 1.119
Comment on publications: PMID: 26545878. 3 unrelated cases (6 individuals), Ashkenazi Jewish families. p.Val54Leu. 4/4 (2 MRI was not reported) delayed myelination and periventricular white matter abnormalities on brain imaging, 5/6 feeding difficulties, 5/6 developmental delay, 5/5 progressively decreasing head circumference percentile (up to -2 SD), 6/6 spasticity, 5/6 increased muscle tone, 1/6 ataxia, 2/6 (same family) optic atrophy, 4/6 nystagmus, 1/6 heart failure, 1/6 perimyocarditis.

PMID: 28000699. Finnish case. Difference variant than what was described in PMID:26545878 (p.Cys4Ser). Diffuse hypomyelination, cystic changes of periventricular white matter, has increased muscle tone, spasticity, ataxia, mild optic atrophy, myopia nystagmus and epilepsy. No feeding difficulties or microcephaly.
Created: 26 May 2021, 2:59 p.m. | Last Modified: 26 May 2021, 2:59 p.m.
Panel Version: 1.118

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Six children from three unrelated Ashkenazi Jewish families reported, segregating same homozygous variant. Neurodegenerative disorder characterized by infantile onset of delayed psychomotor development, axial hypotonia, and spasticity associated with delayed myelination and periventricular white matter abnormalities on brain imaging. Other features: visual impairment; cardiac failure during acute illness.
Sources: Expert list
Created: 15 Sep 2020, noon

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Leukodystrophy, hypomyelinating, 13, MIM# 616881

Publications

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

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Expert Review Amber
Phenotypes
  • Leukodystrophy, hypomyelinating, 13, OMIM:616881
Tags
Q2_21_rating
OMIM
614908
Clinvar variants
Variants in HIKESHI
Penetrance
None
Publications
Panels with this gene

History Filter Activity

27 May 2021, Gel status: 2

Added Tag

Ivone Leong (Genomics England Curator)

Tag Q2_21_rating tag was added to gene: HIKESHI.

26 May 2021, Gel status: 2

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

Ivone Leong (Genomics England Curator)

gene: HIKESHI was added gene: HIKESHI was added to Hereditary spastic paraplegia - childhood onset. Sources: Expert Review Amber,Expert list Mode of inheritance for gene: HIKESHI was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HIKESHI were set to 26545878; 28000699 Phenotypes for gene: HIKESHI were set to Leukodystrophy, hypomyelinating, 13, OMIM:616881