title: A novel MYH7 Leu1453pro mutation resulting in Laing distal myopathy in an Irish family.
abstract: 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.
authors.affiliation: Department of Neurology, Beaumont Hospital, Dublin, Ireland; Department of Neurology, Cork University Hospital, Cork, Ireland. Electronic address: stela_lefter@yahoo.com.
authors.forename: Stela
authors.initials: S
authors.lastname: Lefter
authors.affiliation: Department of Neurology, Beaumont Hospital, Dublin, Ireland.
authors.forename: Orla
authors.initials: O
authors.lastname: Hardiman
authors.affiliation: Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland.
authors.forename: Russell L
authors.initials: RL
authors.lastname: McLaughlin
authors.affiliation: The Adelaide and Meath Hospital Dublin, Incorporating the National Children's Hospital, Dublin, Ireland.
authors.forename: Sinead M
authors.initials: SM
authors.lastname: Murphy
authors.affiliation: Department of Neuropathology, Beaumont Hospital, Dublin, Ireland.
authors.forename: Michael
authors.initials: M
authors.lastname: Farrell
authors.affiliation: Department of Neurology, Cork University Hospital, Cork, Ireland.
authors.forename: Aisling M
authors.initials: AM
authors.lastname: Ryan
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000473:pathology; D024722:Cardiac Myosins / Q000235:genetics*; D003402:Creatine Kinase / Q000097:blood; D049310:Distal Myopathies / Q000097:blood / Q000150:complications / Q000235:genetics*; D004576:Electromyography; D004827:Epilepsy / Q000209:etiology; D005192:Family Health; D005260:Female; D006801:Humans; D007494:Ireland; D007930:Leucine / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D018995:Myosin Heavy Chains / Q000235:genetics*; D011392:Proline / Q000235:genetics*
chemical_list: C501641:MYH7 protein, human; D011392:Proline; D003402:Creatine Kinase; D024722:Cardiac Myosins; D018995:Myosin Heavy Chains; D007930:Leucine
keywords: Brain white matter disease; Epilepsy; Laing distal myopathy; MYH7