Early onset or syndromic epilepsy

Gene: HSPD1

I don't know

Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Red.

Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.

Panel Version: 1.189

Red List (low evidence)

A single large family with brain hypomyelination and leukodystrophy, PMID 18571143. Otherwise, very limited evidence of the effect on HSPD1 mutations.

Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.

Panel Version: 1.188

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Leukodystrophy hypomyelinating 4, 612233; Spastic paraplegia 13, 605280

Comment when marking as ready: HSPD1 remains as an amber gene as there is not enough evidence to promote it to a green gene. I have added the watchlist tag.

Created: 3 Dec 2018, 10:37 a.m.

Comment when marking as ready: Leukodystrophy, hypomyelinating, 4 is associated with HSPD1 on OMIM and Gene2Phenotype, and seizures is listed as a phenotype on both databases. However, there are only 2 reported families with variants in this gene. In one large family (PMID:18571143) of Israeli descent with 6 of 10 affected members who have seizures. In another study (PMID:30083362) one patient (Japanese) with a different variant in HSPD1 also has seizures. I could not access the other publication mentioned by (Zornitza Stark (Australian Genomics)) (PMID: 27405012); however, as the paper reported a patient from the same geographical area as the PMID: 18571143 report who has the same mutation I have not counted this as a third case. Therefore, there is not enough evidence to promote this gene to green.

Created: 15 Nov 2018, 5:23 p.m.

Green List (high evidence)

Seizures are part of the phenotype of this leukodystrophy.

Created: 15 Aug 2018, 2:03 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Leukodystrophy, hypomyelinating, 4, MIM#612233

Publications

• 27405012, 18571143, 30083362

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