Evidence for a dominant-negative effect in ACTA1 nemaline myopathy caused by abnormal folding, aggregation and altered polymerization of mutant actin isoforms.
We have studied a cohort of nemaline myopathy (NM) patients with mutations in the muscle alpha-skeletal actin gene (ACTA1). Immunoblot analysis of patient muscle demonstrates increased gamma-filamin, myotilin, desmin and alpha-actinin in many NM patients, consistent with accumulation of Z line-derived nemaline bodies. We demonstrate that nebulin can appear abnormal secondary to a primary defect in actin, and show by isoelectric focusing that mutant actin isoforms are present within insoluble ...Expand abstract
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