Childhood onset hereditary spastic paraplegia
Gene: HPDLEnsemblGeneIds (GRCh38): ENSG00000186603
EnsemblGeneIds (GRCh37): ENSG00000186603
HPDL is in 10 panels
4 reviews
Sarah Leigh (Genomics England Curator)
The 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
Cristina Dias (The Francis Crick Institute)
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
Arina Puzriakova (Genomics England Curator)
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
Evan Reid (University of Cambridge)
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
Details
- Mode of Inheritance
- BIALLELIC, autosomal or pseudoautosomal
- Sources
-
- Expert Review Green
- 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
- Tags
- Clinvar variants
- Variants in HPDL
- Penetrance
- Complete
- Publications
- Panels with this gene
-
- White matter disorders and cerebral calcification - narrow panel
- Childhood onset hereditary spastic paraplegia
- Intellectual disability
- Likely inborn error of metabolism
- Hereditary neuropathy or pain disorder
- Mitochondrial disorders
- Possible mitochondrial disorder - nuclear genes
- DDG2P
- Early onset or syndromic epilepsy
- Severe microcephaly
History Filter Activity
Added Tag
Eleanor Williams (Genomics England Curator)Tag gene-checked tag was added to gene: HPDL.
Removed Tag, Removed Tag
Ivone Leong (Genomics England Curator)Tag Q2_21_rating was removed from gene: HPDL. Tag Q2_21_NHS_review was removed from gene: HPDL.
Added New Source, Status Update
Ivone Leong (Genomics England Curator)Source Expert Review Green was added to HPDL. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Added Tag
Arina Puzriakova (Genomics England Curator)Tag Q2_21_NHS_review tag was added to gene: HPDL.
Set publications
Sarah Leigh (Genomics England Curator)Publications for gene: HPDL were set to 32707086; 33188300
Set Phenotypes
Arina Puzriakova (Genomics England Curator)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
Set publications
Arina Puzriakova (Genomics England Curator)Publications for gene: HPDL were set to PMID: 32707086; 33188300
Entity classified by Genomics England curator
Arina Puzriakova (Genomics England Curator)Gene: hpdl has been classified as Amber List (Moderate Evidence).
Added Tag
Arina Puzriakova (Genomics England Curator)Tag Q2_21_rating tag was added to gene: HPDL.
Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance
Evan Reid (University of Cambridge)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