STXBP1: the second synaptic vesicle release gene involved in epilepsy

De novo mutations in the gene encoding STXBP1 (MUNC18‐1) cause early infantile epileptic encephalopathy
Saitsu et al. (2008)
Nature Genetics 40: 782–788     

Apoptotic cell death in mouse models of GM2 gangliosidosis and observations on human Tay-Sachs and Sandhoff diseases

Tay-Sachs and Sandhoff diseases are autosomal recessive neurodegenerative diseases resulting from the inability to catabolize GM2 ganglioside by beta-hexosaminidase A (Hex A) due to mutations of the alpha subunit (Tay-Sachs disease) or beta subunit (Sandhoff disease) of Hex A. Hex B (beta beta homodimer) is also defective in Sandhoff disease. We previously developed mouse models of both diseases and showed that Hexa-/- (Tay-Sachs) mice remain asymptomatic to at least 1 year of age while Hexb-/- (Sandhoff) mice succumb to a profound neurodegenerative disease by 4-6 months of age. Here we find that neuron death in Hexb-/- mice is associated with apoptosis occurring throughout the CNS, while Hexa-/- mice were minimally involved at the same age. Studies of autopsy samples of brain and spinal cord from human Tay-Sachs and Sandhoff diseases revealed apoptosis in both instances, in keeping with the severe expression of both diseases. We suggest that neuron death is caused by unscheduled apoptosis, implicating accumulated GM2 ganglioside or a derivative in triggering of the apoptotic cascade.      

Functional consequences of ROMK mutants linked to antenatal Bartter's syndrome and implications for treatment

The antenatal variant of Bartter's syndrome is an autosomal recessive kidney disease characterized by polyhydramnios, premature delivery, hypokalemic alkalosis and hypercalciuria. It is genetically heterogeneous, having been linked recently to mutations in an ATP- sensitive, renal outer medullary K+channel, ROMK, and earlier to mutations in the Na-K-2Cl co-transporter, NKCC2. We characterized four of the mutations reported in three heterozygous ROMK variants of antenatal Bartter's and found that each expressed a distinct phenotype in Sf9 cells. One mutation expressed normal function and appears to be an allelic polymorphism. The other three mutations produced channels with significantly reduced K+fluxes. However, the mechanisms in each case were different and reflected abnormalities in phosphorylation, proteolytic processing or protein trafficking. The different mechanisms may be important in the design of appropriate therapy for patients with this disease.      

The influence of stimulus parameters on the visual field indices by automated projection perimetry

The various stimulus parameters offered by two standard automated projection perimeters [Humphrey Field Analyser 630 (HFA) and Octopus 2011, namely, stimulus size and location and the interaction of adaptation level and stimulus duration, were compared in a sample of 20 patients attending a glaucoma clinic using the visual field indices mean defect (MD), loss variance (LV), short-term fluctuation (SF) and corrected loss variance (CLV). LV and SF were greater with Octopus program 32 compared with Octopus program G1 (P < 0.02). No difference in the indices was found between stimulus sizes I and III for HFA program 30-2. MD was greater for program 30-2 compared with program 32 (P < 0.002) when expressed in terms of log (L/L) whereas LV (P < 0.02) and SF (P < 0.02) were greater for program 32. All differences were considered to be negligible in the clinical sense.     

Neuropsychological fields in early neurotrauma rehabilitation

It meanwhile is commonly accepted that early onset of specific rehabilitation intervention in traumatic brain injured patients will enhance the recovery of brain function. The integration of neuropsychology in the early treatment of traumatic brain injury can mainly be ascribed to the increasing recognition that cognitive, personality and emotional deficits have been the most devasting longterm problems faced by patients and their families. The aim of our paper is to illustrate the role of neuropsychology in the early stage of rehabilitation. Neuropsychological therapy and the application of appropriate tests depend on the level of consciousness and the extent of behavioural problems. Observation, cognitive screening tests and the use of valid neuropsychological tests make up the main approaches. Our rehabilitation program includes measures of sensory and cognitive stimulation. Improvement of attention and stimulation of cognitive functions are one of the most important aims of early neuropsychological therapy. We choose tasks which require automatic information processing, the retrieval of well established knowledge and implicit learning. Appropriate tests and the development of neuropsychological treatment programmes represent an important means of maximising the patient's capacity to benefit from early rehabilitation.