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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 histo ry. Three previously reported and two novel disease-associated MYOT mutations w ere identified in this group of patients. The disease is characterized by the on set at the age of 42-77 years with muscle weakness initially in distal or proxi mal leg muscles, eventually spreading to other muscle groups of the lower and up per extremities. Associated signs of cardiomyopathy, respiratory failure and per ipheral neuropathy are present in a fraction of patients. Myopathological featur es of focal myofibrillar destruction resulting in intracytoplasmic deposits, str ongly immunoreactive to myotilin, multiple rimmed and centrally or subsarcolemma lly located non-rimmed vacuoles and streaming Z-lines, were observed in each p atient studied. The Spanish cohort, the largest group of patients studied so far , shares phenotypic features with both LGMD1A and MFM/MYOT variants thus establi shing a continuum of phenotypic manifestations characteristic of myotilinopathy, an emerging neuromuscular disorder.
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 histo ry. Three previously reported and two novel disease-associated MYOT mutations w ere identified in this group of patients. The disease is characterized by the on set at the age of 42-77 years with muscle weakness initially in distal or proxi mal leg muscles, eventually spreading to other muscle groups of the lower and up per extremities. Associated signs of cardiomyopathy, respiratory failure and per ipheral neuropathy are present in a fraction of patients. Myopathological featur es of focal myofibrillar destruction resulting in intracytoplasmic deposits, str ongly immunoreactive to myotilin , multiple rimmed and centrally or subsarcolemma lly located non-rimmed vacuoles and streaming Z-lines, were obs The Spanish cohort, the largest group of patients studied so far, shares phenotypic features with both LGMD1A and MFM / MYOTFESSION therefore establi shing a continuum of phenotypic manifestations characteristic of myotilinopathy, an emerging neuromuscular disorder.