Episodic Ataxia Type 2 with Downbeating Nystagmus Caused by Mutation in the CACNA1A: A Case Report

Episodic ataxia type 2 (EA 2) is a rare disorder characterized by intermittent episodes of ataxia with interictal nystagmus. The authors report a patient with EA 2, who presented with recurrent episodes of vertigo, gait ataxia and interictal downbeat nystagmus, which had developed about 16 years before. The chromosomal analysis revealed a translocation between chromosome 7 and chromosome 19 (t(7;19)). The break point in chromosome 19 was the P13 locus of the CACNA1A gene.

Change of the Balance Function with Aging: Computerized Dynamic Posturography Study

BACKGROUND: The purpose of this study is to evaluate balance functions as one ages using the values of the sensory organization test (SOT) and the motor control test (MCT) of computerized dynamic posturography (CDP) in healthy Korean adults. METHODS: We studied the equilibrium scores of the SOT and weight symmetries, latencies, and adaptation scores of the MCT in 72 healthy Korean adults. Subjects were divided into three age groups, the 30's (young group), 50's (middle-aged group), and 70's (elderly group). RESULTS: In the SOT, the range of mean equilibrium scores was from 69.8 to 94.2 in the 3rd decade group, 62.6 to 93.8 in the 5th decade group, 59.2 to 91.2 in the 7th decade group. In the MCT, during sudden anterior and posterior perturbations, the weight symmetries were 101.1 +/- 7.5 in the 3rd decade group, 103.6 +/- 6.9 in the 5th decade group, and 106.4 +/- 9.4 in the 7th decade group. The mean latencies were 123.6-132.8 msec in the 3rd decade group, 130.5-138.5 msec in the 5th decade group, 132.7-141.8 msec in the 7th decade group. CONCLUSIONS: Almost all measures of balance were significantly worse in the elderly group compared with the young group and some changes of balance were observed in the middle-aged group as well. These significant age-associated declines of balance function suggested the decreased capacity to process sensory inputs in aged persons. This occurs most likely as a result of biomechanical or central processing changes.

Hyperventilation Induced Nystagmus in Patient with Vestibular Schwannoma : A Case Report

When doctors evaluate the complaints of dizziness, they often perform a series of clinical tests to look for the evidence of a vestibular dysfunction. A useful procedure is to ask the patient to take deep breaths and observe the gaze behind Frenzel goggles. If hyperventilation-induced nystagmus(HIN) is detected, it is the evidence for an underlying vestibular imbalance. The authors evaluated nystagmus with electronystagmography after hyperventilation for 50 seconds. Brain imaging was performed to search the responsible lesion for dizziness. Brain MRI revealed a brain tumor suggesting vestibular schwannoma in the left cerebellopontine angle. After hyperventilation, dizziness and the right beating horizontal nystagmus with Alexander law could be detected. By precisely measuring the HIN, we determined that inputs arising from the horizontal semicircular canal were mainly responsible. The contralaterality of the direction of the horizontal component of the nystagmus was detected. We suggest that clinicians should routinely check the nystagmus after hyperventilation, when they evaluate patients complaining of dizziness.

Cloning and Localization of Developmentally Regulated Gene, Glutamate/Aspartate Transporter (GLAST) Gene, in the Developing Rat Cerebellum / 대한해부학회지

In this study, S59158, a gene of GLAST (L-Glutamate/L-Aspartate transporter), was cloned by ordered differential display PCR with developing rat brains. The mRNA expression of this gene in the developing rat brain and the effect of kainic acid (KA), glutamate analogue, on this gene were investigated with in situ hybridization histochemistry. The expression of S59158 was restricted to nervous system and observed from E12 (embryonic day 12), peaked at E20, and gradually decreased to adult level. In embryos, S59158 was prominently expressed in the subventricular zones throughout the brain. After birth, strong expression was observed in the purkinje cell layer of cerebellum and moderate level of expression was observed in the subventricular zone, olfactory bulb, hippocampal formation, and cerebral cortex. In the KA treated rat brains, the expression of S59158 was significantly increased in dentate gyrus, hippocampus, and cerebral cortex. From these results, it may be suspected that S59158 is related to the development of the brain and is induced by increased extracellular glutamate level.

Genomic structure of the regulatory region of the voltage-gated calcium channel alpha 1D

In excitable and endocrine organs, calcium influxes through the L-type voltage-gated calcium channel (VGCC) which is composed of four (alpha 1, alpha 2, beta, and gamma) subunits. Temporal and spatial expression of calcium channel activity is regulated by the transcription of alpha 1 subunit. To elucidate the genomic organization of the VGCC alpha 1D subunit gene, a genomic clone was isolated from the human genomic library and its sequence was analyzed. A 12 kb genomic clone contained the 5'-flanking regulatory region and first two exons was selected and the initiation site for alpha 1D mRNA synthesis was examined by primer extension analysis. The major initiation site was found at the -523 NT position in the translation initiation site. The TATA box could not be found above the transcription initiation site. The CAT vector construct containing the 2.5 kb upstream region had high CAT activity on transfection to NG108-15 and PC12 cells, which confers the neuronal expression of the alpha 1D gene.

Structure of human voltage-dependent calcium channel (VDCC) beta 3 subunit gene

In excitable and endocrine organs, calcium influxes through the voltage-dependent calcium channel (VDCC), composed of four (alpha 1, alpha 2, beta, and gamma) subunits. Four isoforms of beta subunits (beta 1, beta 2, beta 3, beta 4) are known to exist, The cytoplasmic beta subunits regulate the channel activity by accelerating the kinetics of activation and inactivation through phosphorylation. Regulation of calcium channel activities are also provided by alternative splicing of the beta subunits. To elucidate the genomic organization of the VDCC beta 3 subunit gene, two genomic clones were isolated from human genomic liabrary using the whole rat cDNA for beta 3 subunit as a probe. The beta 3 subunit gene in lamda phage DNA was analyzed by Southern hybridization and sequencing. A 19.1 kb clone (2BHG13) contained the whole beta 3 cDNA sequence, consisting at least 14 exons. The deduced amino acid sequence from the exons shows 97% similarity with that of rat gene. Two alternatively spliced forms of beta 3 subunit at 5'-end were found. The beta 3 subunit had many possible phosphorylation sites. Alternative splicing of beta 3 subunit mRNA at 5'-end and phosphorylation of the beta 3 subunit protein may play a regulatory role in calcium influxes.