title: Expanding the phenotypes of the Pro56Ser VAPB mutation: proximal SMA with dysautonomia.
abstract: The phenotype of 16 members of a family affected by a late-onset, dominant, progressive, motor and autonomic disorder is described. The VAPB (Pro56Ser) mutation was detected in Brazilian families with different phenotypes of motor neuron disorders. In this family, proximal and axial muscle weakness and atrophy, associated with abdominal protrusion, defined the motor phenotype. Death occurred in 10-15 years due to respiratory insufficiency. Tone and tendon reflexes were decreased and a distal tremor was common. Sensation was preserved. Autonomic abnormalities were also present, including choking, chronic intestinal constipation, sexual dysfunction, and sudomotor abnormalities, and on nerve morphology there was involvement of unmyelinated fibers. Electromyography disclosed ongoing denervation and reinnervation. Isolated dysfunction of motor and autonomic neurons is unusual among the spinal muscular atrophies. On this basis, this condition seems to represent a new category of disease.
authors.affiliation: Department of Neurology, School of Medicine of Ribeirão Preto, University of São Paulo, Av. Bandeirantes, 3900 Ribeirão Preto, São Paulo, 14049-900, Brazil.
authors.forename: Vanessa D
authors.initials: VD
authors.lastname: Marques
authors.forename: Amilton A
authors.initials: AA
authors.lastname: Barreira
authors.forename: Mary B
authors.initials: MB
authors.lastname: Davis
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Abou-Sleiman
authors.forename: Wilson A
authors.initials: WA
authors.lastname: Silva
authors.forename: Marco A
authors.initials: MA
authors.lastname: Zago
authors.forename: Claudia
authors.initials: C
authors.lastname: Sobreira
authors.forename: Valéria
authors.initials: V
authors.lastname: Fazan
authors.forename: Wilson
authors.initials: W
authors.lastname: Marques
mesh_terms: D000328:Adult; D001342:Autonomic Nervous System Diseases / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*; D001938:Brazil; D004576:Electromyography; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009134:Muscular Atrophy, Spinal / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011392:Proline / Q000737:chemistry / Q000235:genetics; D012694:Serine / Q000737:chemistry / Q000235:genetics; D033921:Vesicular Transport Proteins / Q000235:genetics*
chemical_list: C496748:VAPB protein, human; D033921:Vesicular Transport Proteins; D012694:Serine; D011392:Proline