Likely inborn error of metabolism

Gene: PNPLA2

Green List (high evidence)

The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.

Created: 11 Oct 2023, 12:32 p.m. | Last Modified: 11 Oct 2023, 12:32 p.m.

Panel Version: 4.51

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next GMS update.

Created: 3 May 2023, 6:12 a.m. | Last Modified: 3 May 2023, 6:12 a.m.

Panel Version: 4.27

There are at least ten unrelated cases of lipid storage disease with myopathy reported in literature with biallelic variants in PNPLA2 gene. Muscle biopsies showed marked neutral lipid accumulation in majority of these cases.

Functional studies in PMID:25287355 showed that expression of PNPLA2 variant plasmids (p.Asp166Gly/ p.Pro481Leu) in HeLa cells resulted in impaired enzyme activity, confirming the pathological effects of the variants.

This gene has also been associated with neutral lipid storage disorder in both OMIM (MIM #610717) and Gene2Phenotype (with 'strong' rating in the DD panel).

Created: 3 May 2023, 6:05 a.m. | Last Modified: 3 May 2023, 6:05 a.m.

Panel Version: 4.25

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neutral lipid storage disease with myopathy, OMIM:610717

Publications

• 18952067
• 21544567
• 25287355
• 25956450
• 32269696

Green List (high evidence)

PLPLA2 is a triglyceride lipase and this is a lipid storage disorder.
Sources: Expert Review

Created: 7 Feb 2021, 3:07 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neutral lipid storage disease with myopathy MIM#610717

Publications

• 18952067
• 25287355
• 25956450