Characterization of these mice revealed that the truncation caused a moderate myopathy phenotype reminiscent of nemaline myopathy despite the majority of nebulin being localized properly in the thin filaments.
Fifty percent of nemaline myopathy forms are due to NEB mutations, but genetic analysis of this large and complex gene by Sanger sequencing is time consuming and expensive.
Mutations in the gene encoding nebulin (NEB) are known to cause several types of congenital myopathy including recessive nemaline myopathy and distal nebulin myopathy.
Mutations in several NM causal genes have been attributed to the majority of NM cases, particularly mutations in nebulin and skeletal muscle α‑actin 1 (ACTA1), which are responsible for ~70% of cases; therefore, a genetic diagnostic strategy using targeted gene sequencing may potentially improve the diagnosis of suspected NM.
Based on biopsy material, genetic analyses and muscle MRI, we identified two novel, compound-heterozygous variants in the nebulin gene after a 30 year clinical history, which cause a classical childhood type of nemaline myopathy.
We describe 3 young patients presenting congenital core-rod myopathy with bilateral foot-drop associated with autosomal recessive nebulin gene (NEB) mutations detected by exome sequencing.
Enhanced utility of family-centered diagnostic exome sequencing with inheritance model-based analysis: results from 500 unselected families with undiagnosed genetic conditions.
Loss of sarcomere thin filament proteins is a frequent cause of NM; therefore, our data that KLHL40 stabilizes NEB and LMOD3 provide a potential basis for the development of NM in KLHL40-deficient patients.