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Severe microcephaly

Gene: HPDL

Green List (high evidence)

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

2 reviews

Sarah Leigh (Genomics England Curator)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Created: 10 Mar 2022, 1:37 p.m. | Last Modified: 10 Mar 2022, 1:37 p.m.
Panel Version: 2.292

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

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: Literature
Created: 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
  • 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
gene-checked
Clinvar variants
Variants in HPDL
Penetrance
None
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.

10 Mar 2022, Gel status: 3

Removed Tag

Eleanor Williams (Genomics England Curator)

Tag Q2_21_rating was removed from gene: HPDL.

10 Mar 2022, Gel status: 3

Added New Source, Status Update

Eleanor Williams (Genomics England Curator)

Source Expert Review Green was added to HPDL. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

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: 1

Created, Added New Source, Added Tag, Set mode of inheritance, Set publications, Set Phenotypes

Arina Puzriakova (Genomics England Curator)

gene: HPDL was added gene: HPDL was added to Severe microcephaly. Sources: Literature Q2_21_rating 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 Review for gene: HPDL was set to GREEN