Early onset or syndromic epilepsy
Gene: HSPD1
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
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.
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
Variants in this GENE are reported as part of current diagnostic practice
Phenotypes for gene: HSPD1 were changed from Leukodystrophy, hypomyelinating, 4, 612233 to Leukodystrophy, hypomyelinating, 4, OMIM:612233
Source Wessex and West Midlands GLH was added to HSPD1.
Source NHS GMS was added to HSPD1.
Zornitza Stark: Seizures are part of the pheno
Gene: hspd1 has been classified as Amber List (Moderate Evidence).
Gene: hspd1 has been classified as Amber List (Moderate Evidence).
Tag watchlist tag was added to gene: HSPD1.
Publications for gene: HSPD1 were set to
Mode of inheritance for gene: HSPD1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: HSPD1 were changed from to Leukodystrophy, hypomyelinating, 4, 612233
Expert Review Amber was added to HSPD1. Panel: Genetic Epilepsy Syndromes
HSPD1 was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
HSPD1 was created by Sarah Leigh