Limb-Girdle Muscular Dystrophy and Distal Myopathy

Gene: ORAI1

I don't know

Variable age of onset and presentation but adult onset, proximal weakness and increased CK all reported, agree sufficient phenotypic overlap.

Created: 1 Jul 2020, 7:30 a.m. | Last Modified: 1 Jul 2020, 7:30 a.m.

Panel Version: 0.35

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Myopathy, tubular aggregate, 2 (MIM#615883)

I don't know

OMIM notes both proximal and diffuse muscle weakness. There is some phenotypic overlap.

PMID 31448844 (comprehensive review, summarises all published cases, references functional evidence): - Dominant ORAI1 missense variants via a GOF mechanism cause a slowly progressive myopathy (tubular aggregate myopathy/TAM)
Sources: Expert Review

Created: 30 Jun 2020, 10:59 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Myopathy, tubular aggregate, 2 (MIM#615883)

Publications

• 31448844

Green List (high evidence)

PMID 31448844 (comprehensive review, summarises all published cases, references functional evidence):
- Dominant ORAI1 missense variants via a GOF mechanism cause a slowly progressive myopathy (tubular aggregate myopathy/TAM)
- Recessive ORAI1 variants via a LOF mechanism cause a combined immunodeficiency (recurrent and chronic infections, autoimmunity, ectodermal dysplasia, non-progressive myopathy)

Created: 20 Apr 2020, 5:58 a.m. | Last Modified: 20 Apr 2020, 6:03 a.m.

Panel Version: 0.2440

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Progressive myopathy; contractures

Publications

• PMID: 31448844

Mode of pathogenicity
Other

Variants in this GENE are reported as part of current diagnostic practice