title: A paucisymptomatic neuromuscular disease mimicking type III 5q-SMA with complex rearrangements in the SMN gene.
abstract: Spinal muscular atrophy is an autosomal-recessive neuromuscular disorder, causing progressive proximal weakness and atrophy of the voluntary muscles. More than 96% of the spinal muscular atrophy patients show a homozygous absence of exons 7 and 8, or exon 7 only, in SMN1, the telomeric copy of the SMN gene. We report a young male patient with neurogenic symptoms and sparse muscle fiber atrophy, suggestive of a mild form of type III spinal muscular atrophy. He was found to be a carrier of intragenic mutations in both copies of the SMN gene, exhibiting a homozygous duplication of exons 7 and 8 in SMN1 and a homozygous deletion of exon 8 as well as a heterozygous deletion of exon 7 in SMN2. However, an intact full-length SMN1 complementary deoxyribonucleic acid was identified, and SMN protein levels in a muscle specimen were identical to that of a healthy control, formally excluding the diagnosis of spinal muscular atrophy III.
authors: 1Department of Neuropathology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors: Laura Nanna
authors: LN
authors: Lohkamp
authors: Katja
authors: K
authors: von Au
authors: Hans-Hilmar
authors: HH
authors: Goebel
authors: Wolfram
authors: W
authors: Kress
authors: Ulrike
authors: U
authors: Grieben
authors: Karin
authors: K
authors: Drossel
authors: Lutz
authors: L
authors: Garbes
authors: Brunhilde
authors: B
authors: Wirth
authors: Frank L
authors: FL
authors: Heppner
authors: Werner
authors: W
authors: Stenzel
mesh_terms: D000818:Animals; D001706:Biopsy; D002648:Child; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D009133:Muscular Atrophy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D009468:Neuromuscular Diseases / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D052097:Quadriceps Muscle / Q000378:metabolism / Q000473:pathology; D017384:Sequence Deletion; D014897:Spinal Muscular Atrophies of Childhood / Q000175:diagnosis* / Q000235:genetics; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics* / Q000378:metabolism; D055540:Survival of Motor Neuron 2 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C526471:SMN1 protein, human; C526477:SMN2 protein, human; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein
keywords:    SMN1 gene;    SMN2 gene; deletion; duplication; spinal muscular atrophy