Abstract
Five affected siblings were referred with a probable diagnosis of proximal adult-type spinal muscular atrophy (SMA) based on lower motor neuron signs (muscle weakness and atrophy, hypotony, hypoactive or absent reflexes, and fasciculations), normal or borderline serum creatine kinase levels, and a neurogenic pattern on electromyography, compatible with motor neuron disease, in one patient. No exon 7-8 deletion in the survival motor neuron (SMN) gene was found. Linkage analysis excluded the SMN and all known autosomal recessive limb girdle muscular dystrophy loci, with the exception of LGMD-2A. A homozygous R769Q mutation in the calpain-3 gene and absence of muscle calpain-3 protein confirmed a calpainopathy. This family suggests that the clinical spectrum of calpainopathy might be broader and that this diagnosis might be considered in patients with an atypical motor neuron disease.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Biopsy
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Calpain / deficiency*
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Calpain / genetics
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Chromosome Mapping
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Cyclic AMP Response Element-Binding Protein
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DNA Mutational Analysis
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Electromyography
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Female
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Gene Deletion
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Genetic Testing
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Genetic Variation / genetics
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Humans
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Isoenzymes*
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Male
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Middle Aged
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Muscle Fibers, Skeletal / enzymology
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Muscle Fibers, Skeletal / pathology
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Muscle Proteins*
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Muscle, Skeletal / enzymology*
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Muscle, Skeletal / pathology
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Muscle, Skeletal / physiopathology
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Muscular Atrophy, Spinal / enzymology*
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Muscular Atrophy, Spinal / genetics*
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Mutation / genetics
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Pedigree
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Phenotype
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RNA-Binding Proteins
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SMN Complex Proteins
Substances
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Cyclic AMP Response Element-Binding Protein
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Isoenzymes
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Muscle Proteins
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Nerve Tissue Proteins
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RNA-Binding Proteins
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SMN Complex Proteins
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CAPN3 protein, human
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Calpain