Hereditary spastic paraplegia - childhood onset

Gene: HPDL

Green List (high evidence)

HPDL (4-hydroxyphenylpyruvate dioxygenase like)
EnsemblGeneIds (GRCh38): ENSG00000186603
EnsemblGeneIds (GRCh37): ENSG00000186603
HPDL is in 6 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
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
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)

Green List (high evidence)

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)

Green List (high evidence)

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)

Green List (high evidence)

Newly identified gene that can give a phenotype ranging from infantile epileptic encephalopathy to juvenile onset progressive spastic paraplegia.
Sources: Literature
Created: 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
gene-checked
Clinvar variants
Variants in HPDL
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

7 May 2022, Gel status: 3

Added Tag

Eleanor Williams (Genomics England Curator)

Tag gene-checked tag was added to gene: HPDL.

14 Mar 2022, Gel status: 3

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.

14 Mar 2022, Gel status: 3

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)

13 Dec 2021, Gel status: 2

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q2_21_NHS_review tag was added to gene: HPDL.

18 May 2021, Gel status: 2

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: HPDL were set to 32707086; 33188300

9 Feb 2021, Gel status: 2

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

9 Feb 2021, Gel status: 2

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: HPDL were set to PMID: 32707086; 33188300

9 Feb 2021, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: hpdl has been classified as Amber List (Moderate Evidence).

9 Feb 2021, Gel status: 0

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q2_21_rating tag was added to gene: HPDL.

4 Feb 2021, Gel status: 0

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