Limb-Girdle Muscular Dystrophy and Distal Myopathy

Gene: DNAJB4

Green List (high evidence)

Emerging evidence of 2 different disease mechanisms: monoallelic distal myopathy may be caused by toxic gain of function and biallelic loss of function with variable onset myopathy with respiratory failure. There is more evidence for the biallelic myopathy with 3 families.
PMID: 36512060 - A single family with distal myopathy segregating a heterozygous missense variant (c.270T>A p.F90L). In vitro functional assays suggest a toxic gain of function mechanism of disease for p.F90L. Both Dnajb4F90L knock-in and Dnafjb4 knockout mice developed muscle weakness
PMID: 36264506 - 4 individuals from 3 unrelated families with myopathy with early respiratory failure with homozygous variants (c.856A > T; p.Lys286Ter, c.74G > A; p.Arg25Gln, c.785 T > C; p.Leu262Ser). DNAJB4 knockout mice had muscle weakness and fibre atrophy with prominent diaphragm involvement and kyphosis, muscle and myotubes had myofibrillar disorganization and accumulated Z-disc proteins and protein chaperones.
Sources: Literature

Created: 14 Apr 2023, 5:39 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
distal myopathy MONDO:0018949; Myopathy, MONDO:0005336, DNAJB4-related

Publications

• 36512060
• 36264506

Green List (high evidence)

4 individuals from 3 unrelated families with bi-allelic LoF/missense variants in this gene, and either childhood/adult onset of muscle weakness and respiratory failure. One had HCM.

Functional studies including mouse model.
Sources: Literature

Created: 3 Nov 2022, 4:09 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Myopathy, MONDO:0005336, DNAJB4-related

Publications

• PMID: 36264506

Green List (high evidence)

4 individuals from 3 unrelated families with bi-allelic LoF/missense variants in this gene, and either childhood/adult onset of muscle weakness and respiratory failure. One had HCM.

Functional studies including mouse model.
Sources: Literature

Created: 3 Nov 2022, 3:59 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Congenital myopathy 21 with early respiratory failure, MIM# 620326