Prepair 1000+

Gene: RBCK1

Green List (high evidence)

Characterized by onset in childhood of progressive proximal muscle weakness, resulting in difficulties in ambulation. Most patients also develop progressive dilated cardiomyopathy, which may necessitate cardiac transplant in severe cases. A small subset of patients present with severe immunodeficiency and a hyperinflammatory state in very early childhood.

A 32kb deletion which included the three last exons of TRIB3 and the first four exons of RBCK1 was identified in one family, also had a nonsense mutation (PMID: 23104095).

The nature and localization of the underlying mutation might predict the phenotype, with N-terminal mutations mainly causing immunological dysfunction. In contrast, variants in the middle- or C-terminal regions were presumed to predominantly cause cardiomyopathy and neuromuscular symptoms. Further, it was suggested that truncating variants might generally result in more severe phenotypes than missense mutations. Frameshift mutations beyond the N-terminus of RBCK1 may lead to a combined phenotype including both myopathy and immunological dysfunction in single families (PMID: 29260357).

Created: 31 Dec 2024, 4:08 a.m. | Last Modified: 31 Dec 2024, 4:34 a.m.

Panel Version: 1.978

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Polyglucosan body myopathy 1 with or without immunodeficiency, MIM #615895

Publications

• PMID: 23104095
• 23798481
• 32187699
• 23889995
• 29260357