Hereditary neuropathy or pain disorder
Gene: HPDLEnsemblGeneIds (GRCh38): ENSG00000186603
EnsemblGeneIds (GRCh37): ENSG00000186603
HPDL is in 10 panels
3 reviews
Sarah Leigh (Genomics England Curator)
The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.Created: 24 Feb 2025, 5:02 p.m. | Last Modified: 24 Feb 2025, 5:02 p.m.
Panel Version: 6.148
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Eleanor Williams (Genomics England Curator)
Comment on list classification: On recommendation of clinical expert this gene has been promoted to amber and has been tagged for promotion to green subject to GMS review.Created: 26 Oct 2024, 10:18 p.m. | Last Modified: 26 Oct 2024, 10:18 p.m.
Panel Version: 5.103
In PubMed:32707086 - Husain et al 2020 - in 13 families (17 individuals) with a progressive, pediatric-onset spastic movement disorder with variable clinical presentation exome sequencing identified biallelic HPDL variants (missense and nonsense). Clinical presentation ranged from severe, neonatal-onset neurodevelopmental delay with neuroimaging findings resembling mitochondrial encephalopathy to milder manifestation of adolescent-onset, isolated hereditary spastic paraplegia. All affected individuals developed spasticity predominantly of the lower limbs over the course of the disease. Demyelinating neuropathy was present in three individuals. HPDL protein level in fibroblasts from severely affected individuals were compared to control fibroblasts and were found to be reduced. In murine cells HPDL co-localizes with the mitochondria, but in patient fibroblasts they did not observe a consistent signature of mitochondrial dysfunction.Created: 26 Oct 2024, 10:17 p.m. | Last Modified: 26 Oct 2024, 10:17 p.m.
Panel Version: 5.102
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, OMIM:619026; Spastic paraplegia 83, autosomal recessive, OMIM:619027; neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, MONDO:0033613; spastic paraplegia 83, autosomal recessive, MONDO:0033614
Publications
Alexander Rossor (UCL Institute of Neurology)
3 had peripheral neuropathy
Sources: Expert listCreated: 19 Oct 2024, 10:41 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
developmental delay; spastic paraplegia; peripheral neuropathy
Publications
Details
- Mode of Inheritance
- BIALLELIC, autosomal or pseudoautosomal
- Sources
-
- Expert Review Green
- NHS GMS
- Phenotypes
-
- Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, OMIM:619026
- Spastic paraplegia 83, autosomal recessive, OMIM:619027
- neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, MONDO:0033613
- 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
Removed Tag, Removed Tag
Sarah Leigh (Genomics England Curator)Tag Q3_24_promote_green was removed from gene: HPDL. Tag Q3_24_NHS_review was removed from gene: HPDL.
Added New Source, Added New Source, Status Update
Sarah Leigh (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
Achchuthan Shanmugasundram (Genomics England Curator)Tag gene-checked tag was added to gene: HPDL.
Added Tag, Added Tag
Eleanor Williams (Genomics England Curator)Tag Q3_24_promote_green tag was added to gene: HPDL. Tag Q3_24_NHS_review tag was added to gene: HPDL.
Set Phenotypes
Eleanor Williams (Genomics England Curator)Phenotypes for gene: HPDL were changed from developmental delay; spastic paraplegia; peripheral neuropathy to Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, OMIM:619026; Spastic paraplegia 83, autosomal recessive, OMIM:619027; neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, MONDO:0033613; spastic paraplegia 83, autosomal recessive, MONDO:0033614
Entity classified by Genomics England curator
Eleanor Williams (Genomics England Curator)Gene: hpdl has been classified as Amber List (Moderate Evidence).
Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance
Alexander Rossor (UCL Institute of Neurology)gene: HPDL was added gene: HPDL was added to Hereditary neuropathy or pain disorder. Sources: Expert list Mode of inheritance for gene: HPDL was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HPDL were set to 32707086 Phenotypes for gene: HPDL were set to developmental delay; spastic paraplegia; peripheral neuropathy Penetrance for gene: HPDL were set to Complete Review for gene: HPDL was set to GREEN