A novel MYH7 Leu1453pro mutation resulting in Laing distal myopathy in an Irish family.

Authors describe clinical, pathological, imaging and genetic findings in the first Irish family with Laing distal myopathy in whom a novel mutation in the human slow β-myosin heavy chain (MYH7) gene has been identified. A kindred of 14 over 6 generations included 6 individuals with childhood onset distal lower limb weakness in a scapula-peroneal distribution with subsequent proximal upper and lower limb weakness. Finger extensor weakness especially in the 3rd-5th fingers was present in each and two patients had "hanging big toe" sign. Three patients were non-ambulatory by middle-age. One patient developed cardiomyopathy and two patients had respiratory muscle impairment. Intriguingly, brain white matter lesions and epilepsy were present in three patients. Muscle biopsy revealed fibre-size variation, rimmed vacuoles, mild-extensive central nucleation, redundant and folded sarcolemmal membrane and Z band streaming. Genetic analysis revealed a novel heterozygous mutation in the MYH7 gene in one patient which co-segregated perfectly in the remaining 5 affected members and was absent in six unaffected members.