White matter disorders and cerebral calcification - narrow panel
Gene: HPDLEnsemblGeneIds (GRCh38): ENSG00000186603
EnsemblGeneIds (GRCh37): ENSG00000186603
HPDL is in 10 panels
3 reviews
Achchuthan Shanmugasundram (Genomics England Curator)
The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.Created: 24 Feb 2025, 6:21 p.m. | Last Modified: 24 Feb 2025, 6:21 p.m.
Panel Version: 6.4
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Sarah Leigh (Genomics England Curator)
Biallelic HPDL variants have been associated with Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (OMIM:619026) and Spastic paraplegia 83, autosomal recessive (OMIM:619027) in OMIM and as a Strong gene for HPDL Neurodegenerative Disease in Gen2Phen.
PMIDs 32707086 and 33188300 report white matter changes in 16/28 individuals from 9/18 families where MRI assessments were available.Created: 22 Aug 2023, 10:37 a.m. | Last Modified: 22 Aug 2023, 10:37 a.m.
Panel Version: 3.16
Comment on list classification: There is enough evidence for this gene to be Green at the next major review.Created: 22 Aug 2023, 10:21 a.m. | Last Modified: 22 Aug 2023, 10:21 a.m.
Panel Version: 3.16
Arina Puzriakova (Genomics England Curator)
Comment on list classification: HPDL was added to this panel following clinical feedback from Helen Brittain (Genomics England Clinical Team). There is enough evidence for this gene to be rated Green at the next major review.Created: 9 Feb 2021, 4:29 p.m. | Last Modified: 9 Feb 2021, 4:38 p.m.
Panel Version: 2.102
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. Microcephaly of relevant severity (HC ≤ 3 SD) was observed in 13/30 cases.
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.
Sources: LiteratureCreated: 9 Feb 2021, 4:25 p.m.
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
Details
- Mode of Inheritance
- BIALLELIC, autosomal or pseudoautosomal
- Sources
-
- Expert Review Green
- NHS GMS
- Literature
- 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
- Tags
- Clinvar variants
- Variants in HPDL
- Penetrance
- None
- 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
Removed Tag
Achchuthan Shanmugasundram (Genomics England Curator)Tag Q3_24_promote_green was removed from gene: HPDL.
Added New Source, Added New Source, Status Update
Achchuthan Shanmugasundram (Genomics England Curator)Source NHS GMS was added to HPDL. Source Expert Review Green was added to HPDL. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Added Tag
Eleanor Williams (Genomics England Curator)Tag Q3_24_promote_green tag was added to gene: HPDL.
Added Tag
Achchuthan Shanmugasundram (Genomics England Curator)Tag gene-checked tag was added to gene: HPDL.
Removed Tag
Sarah Leigh (Genomics England Curator)Tag gene-checked was removed from gene: HPDL.
Entity classified by Genomics England curator
Sarah Leigh (Genomics England Curator)Gene: hpdl has been classified as Amber List (Moderate Evidence).
Created, Added New Source, Added Tag, Set mode of inheritance, Set publications, Set Phenotypes
Sarah Leigh (Genomics England Curator)gene: HPDL was added gene: HPDL was added to White matter disorders and cerebral calcification - narrow panel. Sources: Literature,Expert Review Green gene-checked tags were added to gene: HPDL. Mode of inheritance for gene: HPDL was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HPDL were set to 32707086; 33188300 Phenotypes for gene: HPDL were set 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