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Intellectual disability

Gene: HPDL

Amber List (moderate evidence)

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

2 reviews

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, 2:57 p.m. | Last Modified: 9 Feb 2021, 2:57 p.m.
Panel Version: 3.769
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. 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. Intellectual impairment was reported in 27/32 cases (extent of ID: 10 mild; 1 moderate; 8 severe; 8 unknown severity), with most individuals presenting with minimal to absent psychomotor development.

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, 2:54 p.m. | Last Modified: 9 Feb 2021, 2:54 p.m.
Panel Version: 3.767

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

Evan Reid (University of Cambridge)

Green List (high evidence)

Newly identified gene that can give a phenotype ranging from infantile epileptic encephalopathy with severe developmental delay/intellectual disability to juvenile onset progressive spastic paraplegia.
Sources: Literature
Created: 4 Feb 2021, 3:13 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
spastic paraplegia; spastic tetraplegia; microcephaly; brain atrophy; epilepsy; severe intellectual; motor disability

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
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
Q2_21_rating
Clinvar variants
Variants in HPDL
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

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

Set publications

Arina Puzriakova (Genomics England Curator)

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

9 Feb 2021, Gel status: 0

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q2_21_rating tag was added to gene: HPDL.

9 Feb 2021, Gel status: 0

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: HPDL were changed from spastic paraplegia; spastic tetraplegia; microcephaly; brain atrophy; epilepsy; severe intellectual; 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

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 Intellectual disability. 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; motor disability Penetrance for gene: HPDL were set to Complete Review for gene: HPDL was set to GREEN