title: Calpainopathy: how broad is the spectrum of clinical variability?
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.
authors.affiliation: Human Genome Research Center, Department of Biology, University of São Paulo, São Paulo, Brazil.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Starling
authors.forename: Flavia
authors.initials: F
authors.lastname: de Paula
authors.forename: Helga
authors.initials: H
authors.lastname: Silva
authors.forename: Mariz
authors.initials: M
authors.lastname: Vainzof
authors.forename: Mayana
authors.initials: M
authors.lastname: Zatz
mesh_terms: D000328:Adult; D001706:Biopsy; D002154:Calpain / Q000172:deficiency* / Q000235:genetics; D002874:Chromosome Mapping; D017362:Cyclic AMP Response Element-Binding Protein; D004252:DNA Mutational Analysis; D004576:Electromyography; D005260:Female; D017353:Gene Deletion; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D007527:Isoenzymes; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000201:enzymology / Q000473:pathology; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D009134:Muscular Atrophy, Spinal / Q000201:enzymology* / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010375:Pedigree; D010641:Phenotype; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D007527:Isoenzymes; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; C105884:CAPN3 protein, human; D002154:Calpain