Optic neuropathy

Gene: HIKESHI

Green List (high evidence)

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

Created: 6 Dec 2024, 12:04 p.m. | Last Modified: 6 Dec 2024, 12:04 p.m.

Panel Version: 4.40

Comment on list classification: There is sufficient evidence (3 unrelated cases) available now for promoting this gene to green rating at the next GMS review.

Created: 4 Aug 2023, 5:48 p.m. | Last Modified: 4 Aug 2023, 5:48 p.m.

Panel Version: 4.10

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

New paper since last reviewed (PMID: 34111619) - seven additional, previously unreported affected individuals, including one with optic atrophy, and another with optic nerve pallor. Unrelated to each other, both from Ashkenazi Jewish population

Created: 28 Jul 2023, 2:10 p.m. | Last Modified: 28 Jul 2023, 2:10 p.m.

Panel Version: 4.5

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Leukodystrophy, hypomyelinating

Publications

• 34111619

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 currently not enough evidence to support a gene-disease association (only 2 cases with optic atrophy), therefore this gene has been given an Amber rating.

Created: 26 May 2021, 3:16 p.m. | Last Modified: 26 May 2021, 3:29 p.m.

Panel Version: 2.41

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

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

• 26545878

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