Childhood onset hereditary spastic paraplegia
Gene: HPDLThe rating of this gene has been updated following NHS Genomic Medicine Serviceapproval.Created: 14 Mar 2022, 1:30 p.m. | Last Modified: 14 Mar 2022, 1:30 p.m.
Panel Version: 2.130
Clinical and experimental evidence (in vitro and mouse in vivo) for pathogenicity.Created: 4 May 2021, 9:07 a.m. | Last Modified: 4 May 2021, 9:07 a.m.
Panel Version: 2.28
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
microcephaly; spastic paraplegia; seizures; demyelinating neuropathy; regression; developmental delay; chronic progression; movement disorder
Publications
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, 3:18 p.m. | Last Modified: 9 Feb 2021, 3:18 p.m.
Panel Version: 2.26
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. All affected individuals developed spasticity predominantly of the lower limbs over the course of the disease (with exceptions in PMID:33188300 of 2 individuals from families 4 and 7 who did not present spasticity, and family 3 for whom this information was not available).
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, 3:18 p.m. | Last Modified: 9 Feb 2021, 3:18 p.m.
Panel Version: 2.25
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; Spastic paraplegia 83, autosomal recessive, OMIM:619027; Spastic paraplegia 83, autosomal recessive, MONDO:0033614
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, 3:11 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
spastic paraplegia; spastic tetraplegia; microcephaly; brain atrophy; epilepsy; severe intellectual and motor disability
Publications
Tag gene-checked tag was added to gene: HPDL.
Tag Q2_21_rating was removed from gene: HPDL. Tag Q2_21_NHS_review 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)
Tag Q2_21_NHS_review tag was added to gene: HPDL.
Publications for gene: HPDL were set to 32707086; 33188300
Phenotypes for gene: HPDL were changed from spastic paraplegia; spastic tetraplegia; microcephaly; brain atrophy; epilepsy; severe intellectual and 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; Spastic paraplegia 83, autosomal recessive, OMIM:619027; Spastic paraplegia 83, autosomal recessive, MONDO:0033614
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 Hereditary spastic paraplegia - childhood onset. 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 and motor disability Penetrance for gene: HPDL were set to Complete Review for gene: HPDL was set to GREEN