Expanding the phenotypes of the Pro56SerVAPBmutation: 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.

Protrudin Regulates Endoplasmic Reticulum Morphology and Function Associated with the Pathogenesis of Hereditary Spastic Paraplegia

“…Kif5 also regulates transport of cargo in dendrites and functions in several different membrane trafficking pathways. A VAP mutant that gives rise to familial ALS (ALS8) has been found to induce ER restructuring, providing further support for a role of aberrant ER morphogenesis in neurological disorders (31,32). In addition, VAP contributes to tethering between the ER and the plasma membrane (33)(34)(35).…”

A histomorphometric study of unmyelinated fibers of the fibular nerve in Wistar rats

“…The internal fascicular area measures (mm 2 ) were similar to those obtained in semithin sections, and so we measured fascicular area in semithin sections (Figure 4). The methods that we used in this study are as reliable or more reliable than those used in our previous studies [23][24][25][26] . We represented the frequency distribution of the unmyelinated axons as a histogram, with axon diameters separated into class intervals increasing by 0.2 μm.…”

Spontaneous activity in electromyography may differentiate certain benign lower motor neuron disease forms from amyotrophic lateral sclerosis

“…Several reports have described EMG-recorded spontaneous activity in ALS, but there is less detailed information regarding EMG findings in other motor neuron disorders [3,8,10,14,17,22]. Fibrillations in ALS patients are known to occur more often in weak than non-weak and in distal more frequently than in proximal muscles [15].…”