Likely inborn error of metabolism

Gene: HPDL

Comment on list classification: HPDL has already been promoted to green rating on Mitochondrial disorders panel (https://panelapp.genomicsengland.co.uk/panels/112/gene/HPDL/) as detailed in the below reviews copied from that panel.

As there is sufficient evidence available for the gene-disease association and HPDL is suggested to have a potential role in mitochondrial metabolism, this gene can be promoted to green rating on this panel in the next GMS update.

Created: 7 Jun 2025, 9:18 p.m. | Last Modified: 7 Jun 2025, 9:27 p.m.

Panel Version: 8.24

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 2 May 2024, 10:34 a.m. | Last Modified: 2 May 2024, 10:34 a.m.

Panel Version: 6.3

The to_be_confirmed_NHSE tag has been added, as further NHSE review is required.

Created: 15 Mar 2022, 3:38 p.m. | Last Modified: 15 Mar 2022, 3:38 p.m.

Panel Version: 2.92

Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 16 variants reported in 17 cases from 11 unrelated families, supportive functional studies were reported, including localization of HPDL protein to the mitochrondria and muscle fibre abnormalies in some cases tested (PMID 32707086).

Created: 26 Jan 2021, 11:20 a.m. | Last Modified: 9 Feb 2021, 3:43 p.m.

Panel Version: 2.14

Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.

Created: 26 Jan 2021, 10:49 a.m. | Last Modified: 26 Jan 2021, 10:49 a.m.

Panel Version: 2.14

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Biallelic variants reported in 13 families with a neurodegenerative disease ranging from neonatal encephalopathy to adolescent-onset spastic paraplegia. HPDL has a mitochondrial localization signal and consequently localizes to mitochondria suggesting a putative role in mitochondrial metabolism. Suggest adding to ID panel and possibly others.
Sources: Literature

Created: 4 Aug 2020, 10:46 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Leigh-like phenotype; progressive neurological disease

Publications

• 32707086