Early onset or syndromic epilepsy
Gene: HPDLThe rating of this gene has been updated followingNHS Genomic Medicine Serviceapproval.Created: 11 Mar 2022, 3:31 p.m. | Last Modified: 11 Mar 2022, 3:31 p.m.
Panel Version: 2.498
Comment on list classification: New gene added by Evan Reid (University of Cambridge). There is enough evidence for this gene to be rated Green at the next major review.Created: 9 Feb 2021, 3:30 p.m. | Last Modified: 9 Feb 2021, 3:30 p.m.
Panel Version: 2.290
Associated with relevant phenotype in OMIM and has a 'probable' disease confidence for 'HPDL Neurodegenerative Disease' in Gene2Phenotype.
At least 34 cases from 21 unrelated families with a paediatric-onset spastic movement disorder and biallelic variants in this gene (PMIDs: 32707086 and 33188300). There is broad clinical variability ranging from severe, neonatal-onset neurodevelopmental delay with neuroimaging findings resembling mitochondrial encephalopathy to milder manifestation of adolescent-onset, isolated HSP. Epilepsy were observed in 20/34 cases - phenotypes were not defined in PMID:32707086 but subjects from PMID:33188300 developed seizures within the first year of life that were typically myoclonic, focal, or tonic and occurred daily to weekly.
Supportive functional studies were reported, including localization of HPDL protein to the mitochondria and muscle fibre abnormalities and a KO mouse model displaying features of seizures, early lethality, smaller brain sizes, and cellular apoptosis.Created: 9 Feb 2021, 3:29 p.m. | Last Modified: 9 Feb 2021, 3:29 p.m.
Panel Version: 2.289
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, OMIM:619026; Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, MONDO:0033613
Publications
Newly identified gene that can give a phenotype ranging from infantile epileptic encephalopathy to juvenile onset progressive spastic paraplegia.
Sources: LiteratureCreated: 4 Feb 2021, 3:13 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
spastic paraplegia; spastic tetraplegia; microcephaly; brain atrophy; epilepsy; severe intellectual; motor disability
Publications
Tag gene-checked tag was added to gene: HPDL.
Tag Q2_21_rating was removed from gene: HPDL.
Source Expert Review Green was added to HPDL. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Phenotypes for gene: HPDL were changed from spastic paraplegia; spastic tetraplegia; microcephaly; brain atrophy; epilepsy; severe intellectual; motor disability to Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, OMIM:619026; Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, MONDO:0033613
Publications for gene: HPDL were set to PMID: 32707086; 33188300
Gene: hpdl has been classified as Amber List (Moderate Evidence).
Tag Q2_21_rating tag was added to gene: HPDL.
gene: HPDL was added gene: HPDL was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: HPDL was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HPDL were set to PMID: 32707086; 33188300 Phenotypes for gene: HPDL were set to spastic paraplegia; spastic tetraplegia; microcephaly; brain atrophy; epilepsy; severe intellectual; motor disability Penetrance for gene: HPDL were set to Complete Review for gene: HPDL was set to GREEN