Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies

Gene: PNPLA2

Green List (high evidence)

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

Created: 5 Dec 2024, 5:12 p.m. | Last Modified: 5 Dec 2024, 5:12 p.m.

Panel Version: 4.40

As reviewed by Zornitza Stark (Australian Genomics), there is sufficient number of cases associating PNPLA2 to muscle and upper and lower limb weakness and dystrophy of shoulder girdle. Hence, this gene can be promoted to GREEN at the next GMS update.

This gene has also been associated with phenotypes in both OMIM (MIM #610717) and Gene2Phenotype (with 'strong' rating in DD panel).

Created: 2 May 2023, 8:20 p.m. | Last Modified: 2 May 2023, 8:20 p.m.

Panel Version: 4.13

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neutral lipid storage disease with myopathy, OMIM:610717

Publications

• 18952067
• 21544567
• 25956450
• 32269696

Green List (high evidence)

PMID: 32269696 - 1 patient with both upper and lower limb weakness. She had elevated CK levels, with onset >25 years old.

PMID: 21544567 - 6 patients with distal muscle weakness, shoulder girdle weakness and elevated CK levels. Severe dystrophic features of the shoulder girdle noted in 3/3 patients analysed by whole body MRI. Proximal muscle weakness was generalised first, with lower limbs affected in the 3rd/4th decade of life. Earliest age of onset 29 years old, 5/6 patients had homozygous PTCs.

Phenotypic overlap with LGMD.
Sources: Expert list

Created: 29 Jun 2020, 10:58 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neutral lipid storage disease with myopathy 610717

Publications

• 32269696
• 21544567