Journal Article

Myotilinopathy: refining the clinical and myopathological phenotype

Montse Olivé, Lev G. Goldfarb, Alexey Shatunov, Dirk Fischer and Isidro Ferrer

in Brain

Published on behalf of The Guarantors of Brain

Volume 128, issue 10, pages 2315-2326
Published in print October 2005 | ISSN: 0006-8950
Published online June 2005 | e-ISSN: 1460-2156 | DOI:
Myotilinopathy: refining the clinical and myopathological phenotype

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Mutations in myotilin gene (MYOT) have been associated with variable syndromes including limb girdle muscular dystrophy type 1A (LGMD1A) and a subgroup of myofibrillar myopathy (MFM/MYOT). We studied six Spanish patients from three unrelated kindreds and seven patients without family history. Three previously reported and two novel disease-associated MYOT mutations were identified in this group of patients. The disease is characterized by the onset at the age of 42–77 years with muscle weakness initially in distal or proximal leg muscles, eventually spreading to other muscle groups of the lower and upper extremities. Associated signs of cardiomyopathy, respiratory failure and peripheral neuropathy are present in a fraction of patients. Myopathological features of focal myofibrillar destruction resulting in intracytoplasmic deposits, strongly immunoreactive to myotilin, multiple rimmed and centrally or subsarcolemmally located non-rimmed vacuoles and streaming Z-lines, were observed in each patient studied. The Spanish cohort, the largest group of patients studied so far, shares phenotypic features with both LGMD1A and MFM/MYOT variants thus establishing a continuum of phenotypic manifestations characteristic of myotilinopathy, an emerging neuromuscular disorder.

Keywords: LGMD1A; myofibrillar myopathy; myotilin; MYOT mutations; phenotype; CK = creatinine kinase; EKG = electrocardiography; EMG = electromyography; IBM = inclusion body myositis; LGMD1A = limb girdle muscular dystrophy type 1A; MFM = myofibrillar myopathy; MYOT = myotilin gene; MRC = Medical Research Council; MHC = major histocompatibilty complex; RBBB = right bundle branch block; ZASP = Z-band alternatively spliced PDZ motif-containing protein

Journal Article.  5597 words.  Illustrated.

Subjects: Neurology ; Neuroscience

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