Limb-Girdle Muscular Dystrophy and Distal Myopathy

Gene: CRYAB

Green List (high evidence)

Green for Cataract:
Established association. No correlation for AD versus AR. Variable expressivity reported and unaffected carriers in AR families

Amber for Myopathy:
Recurrent founder variant observed in 8 individuals. Note mono-allelic variants cause an adult-onset milder myopathy.
1x monozygotic twins het for a PTC variant

Red for DCM

Created: 4 May 2022, 10:58 a.m. | Last Modified: 4 May 2022, 10:58 a.m.

Panel Version: 0.13735

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Cataract 16, multiple types MIM#613763 AD, AR; Myopathy, myofibrillar, 2 MIM#608810 AD; Myopathy, myofibrillar, fatal infantile hypertonic, alpha-B crystallin-related MIM#613869 AR

Publications

• 31215171
• 21337604
• 21130652
• 32420686
• 33272090

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

I don't know

Adult onset, proximal weakness and raised CK reported in dominant condition associated with this gene, sufficient phenotypic overlap.

Created: 1 Jul 2020, 7:48 a.m. | Last Modified: 1 Jul 2020, 7:48 a.m.

Panel Version: 0.39

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Myopathy, myofibrillar, 2, MIM# 608810

I don't know

PMID: 21337604 - 8 children with the same homozygous founder mutation and infantile onset muscular dystrophy. Truncal muscles reported to be more affected than limb muscles, phenotype was recapitulated in mouse models.

PMID: 32420686 - monozygotic twin boys with a heterozygous PTC mutation. Patients showed congenital hypotonia, slightly elevated CK levels. Focal signs of muscle degeneration were observed, no particular mention of the location of muscle weakness.
Sources: Expert list

Created: 1 Jul 2020, 1:13 a.m.

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Phenotypes
Myopathy, myofibrillar, 2 608810; Myopathy, myofibrillar, fatal infantile hypertonic, alpha-B crystallin-related 613869

Publications

• PMID: 21337604
• 32420686

I don't know

Biallelic variants cause a severe early onset form of CRYAB-related myopathy. Patients presented with hypertonia (not hypotonia) 3 variants reported to date. Left as amber for now pending additional reports.

PMID: 21337604: Same homozygous variant reported in 8 individuals

PMID: 31215171: 1 patient reported with a start loss variant. Heterozygous parents unaffected. Variant is present in gnomad (14 heterozygotes; 1 homozygote). Functional studies performed on muscle biopsy consistent with myogenic myopathy.

PMID: 21130652: 1 family reported. Variant not present in gnomad

Created: 17 Jun 2020, 2:21 a.m. | Last Modified: 17 Jun 2020, 2:28 a.m.

Panel Version: 0.219

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Myopathy, myofibrillar, fatal infantile hypertonic, alpha-B crystallin-related (MIM#613869)

Publications

• 31215171
• 21337604
• 21130652