Eun Hye Jeong

Technological development of structural DNA/RNA-based RNAi systems and their applications ☆

RNA interference (RNAi)-based gene therapy has drawn tremendous attention due to its highly specific gene regulation by selective degradation of any target mRNA. There have been multiple reports regarding the development of various cationic materials for efficient siRNA delivery, however, many studies still suffer from the conventional delivery problems such as suboptimal transfection performance, a lack of tissue specificity, and potential cytotoxicity. Despite the huge therapeutic potential of siRNAs, conventional gene carriers have failed to guarantee successful gene silencing in vivo, thus not warranting clinical trials. The relatively short double-stranded structure of siRNAs has resulted in uncompromising delivery formulations, as well as low transfection efficiency, compared with the conventional nucleic acid drugs such as plasmid DNAs. Recent developments in structural siRNA and RNAi nanotechnology have enabled more refined and reliable in vivo gene silencing with multiple advantages over naked siRNAs. This review focuses on recent progress in the development of structural DNA/RNA-based RNAi systems and their potential therapeutic applications. In addition, an extensive list of prior reports on various RNAi systems is provided and categorized by their distinctive molecular characters.

Mutational analysis of whole mitochondrial DNA in patients with MELAS and MERRF diseases

Mitochondrial diseases are clinically and genetically heterogeneous disorders, which make the exact diagnosis and classification difficult. The purpose of this study was to identify pathogenic mtDNA mutations in 61 Korean unrelated families (or isolated patients) with MELAS or MERRF. In particular, the mtDNA sequences were completely determined for 49 patients. From the mutational analysis of mtDNA obtained from blood, 5 confirmed pathogenic mutations were identified in 17 families, and 4 unreported pathogenically suspected mutations were identified in 4 families. The m.3243A>G in the tRNALeu(UUR) was predominantly observed in 10 MELAS families, and followed by m.8344A>G in the tRNALys of 4 MERRF families. Most pathogenic mutations showed heteroplasmy, and the rates were considerably different within the familial members. Patients with a higher rate of mutations showed a tendency of having more severe clinical phenotypes, but not in all cases. This study will be helpful for the molecular diagnosis of mitochondrial diseases, as well as establishment of mtDNA database in Koreans.

Ginkgotoxin Induced Seizure Caused by Vitamin B6 Deficiency

Although ginkgo is commonly used as an alternative treatment for memory loss, Alzheimer’s dementia and peripheral circulatory disturbances, it is also known to cause neuronal symptoms due to ginkgotoxin (4′-methoxypyridoxine or B6 antivitamin). We experienced a case of a 51-year-old female patient with generalized tonic clonic seizure and postictal confusion after eating large amounts of ginkgo nuts. Blood vitamin B6 level was decreased. After conservative treatment and pyridoxine medication, her mental symptoms were resolved completely and no seizures recurred.

Enzymatic Synthesis of Self-assembled Dicer Substrate RNA Nanostructures for Programmable Gene Silencing

Enzymatic synthesis of RNA nanostructures is achieved by isothermal rolling circle transcription (RCT). Each arm of RNA nanostructures provides a functional role of Dicer substrate RNA inducing sequence specific RNA interference (RNAi). Three different RNAi sequences (GFP, RFP, and BFP) are incorporated within the three-arm junction RNA nanostructures (Y-RNA). The template and helper DNA strands are designed for the large-scale in vitro synthesis of RNA strands to prepare self-assembled Y-RNA. Interestingly, Dicer processing of Y-RNA is highly influenced by its physical structure and different gene silencing activity is achieved depending on its arm length and overhang. In addition, enzymatic synthesis allows the preparation of various Y-RNA structures using a single DNA template offering on demand regulation of multiple target genes.

Asterixis in the leg induced by anterior cerebral artery infarction

Asterixis commonly occurs in a patient with metabolic encephalopathy, whereas focal brain lesions such as thalamus, cerebellum, or frontal area also cause focal or unilateral asterixis in the arms. We report a novel case of asterixis in the leg after unilateral anterior cerebral artery territory infarction. A 76-year-old man was admitted with sudden-onset mild right leg weakness and postural instability due to knee buckling. He was diagnosed with ischemic stroke in the left prefrontal area and cingulated gyrus by brain magnetic imaging. Needle electromyography of the right vastus lateralis muscle while standing showed intermittent periods of EMG silence, consistent with asterixis. There were no abnormal involuntary movements in the upper extremities. This case suggests that gait disturbance or postural instability after structural lesions in the prefrontal area may be directly related to asterixis in the leg, not in the arm associated with postural failure.

Cerebral Infarction Caused by Cerebral Venous Thrombosis Associated with Iron Deficiency Anemia

Cerebral venous thrombosis (CVT) is a rare condition and has a wide spectrum of symptoms, which makes it difficult to diagnose. CVT has been reported to be associated with various etiologies. However, there are few reported cases of CVT in association with iron deficiency anemia (IDA). Here we report a case of venous infarction caused by CVT associated with IDA. The patient had a good prognosis after iron supplementation and anticoagulation therapy. Since IDA can potentially cause CVT, treatment for IDA may be an important strategy to prevent cerebral infarction caused by CVT.

Valproic Acid-induced Hyperammonemic Encephalopathy Promoted by Levetiracetam

Encephalopathy resulting from the administration of levetiracetam (LEV) is a rare occurrence. We experienced a patient receiving LEV treated with valproic acid (VPA) for partial seizures with secondary generalization, following which she developed hyperammonemic encephalopathy and showed complete recovery after the drug was withdrawan. LEV is able to promote hyperammonemic encephalopathy when added to VPA.

Isolated Mitochondrial Myopathy Misdiagnosed as Polymyositis

Mitochondrial myopathies are caused by dysfunction of the mitochondria and are systemic disorders that present with diverse clinical manifestations. They have been found to be especially prevalent in children. In this report, we present the case of a 55-year-old male patient who developed progressive symmetric proximal muscle weakness in both upper and lower extremities. Although the elevated levels of muscle enzymes and the findings of magnetic resonance imaging of lower extremities were suggestive of polymyositis, we made a final diagnosis of isolated mitochondrial myopathy based on the result of the biopsy of the thigh muscle. In this report, we emphasize the importance of performing a correct differential diagnosis of myopathies, particularly in the cases without evidence of involvement of other organs. *Corresponding author: Eun Hye Jeong, M.D., Department of Neurology, Bundang Jesaeng General Hospital, 20, Seohyeon-ro180beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, Korea, E-mail: gracej3@naver.com Received Date: September 14, 2016 Accepted Date: October 24, 2016 Published Date: October 31, 2016 Citation: Jeong, E.H. et al. Isolated Mitochondrial Myopathy Misdiagnosed as Polymyositis. (2016) Int J Neuro Brain Dis 3(4): 14. Int J Neurol Brain Disord | Volume 3: Issue 4 www.ommegaonline.org

Cerebral infarction caused by a tortuous subclavian artery: a case report.

Tortuous arteries are common clinical observation. Although mild tortuosity is asymptomatic, severe tortuosity can lead to ischemic attack in several organs. With advances in imaging technology, an increasing number of tortuous vessels have been detected. The purpose of this report is to describe a case of acute cerebral infarction due to tortuous subclavian artery and to review the literature.

PO7.9 Phenotypes of 117 Korean Patients with Mitochondrial Disorders

Background: Ventilatory failure is a common and potentially lifethreatening complication of myotonic dystrophy. It usually parallels the muscular manifestations, but there are some cases that ventilatory failure is a presenting symptom without limb weakness. In that case, muscular dysfunction alone is insufficient to account for the ventilatory failure. Case report: A 34-year-old man with history of diabetes and hypercholesterolemia presented to the hospital with a 2-month history of gradually progressive hypersomnia and supine dyspnea. In the emergency room, he was cyanotic and confused, so he was intubated and admitted to intensive care unit. He was obese (BMI: 32.7) and had facial features characteristic of myotonic dystrophy including frontal boldness, hatched face, without ptosis, facial drooping and limb atrophy. Neurologic examination demonstrated mild generalized weakness (MRC grade IV+) and percussion myotonia. Deep tendon reflex were hypoactive, and sensation was normal. Arterial blood gas analysis demonstrated severe hypoxia and hypercapnia with a respiratory acidosis. No cardiac, pulmonary and pharmacologic causes were identified. Pulmonary function tests revealed a severe restrictive ventilatory insufficiency. Electromyography showed myotonic discharges and genetic analysis showed classic phenotype of myotonic dystrophy type 1. Polysomnographic study revealed sleep apnea of central origin. He responded to ventrilatory support with BIPAP. Conclusions: We report a case of myotonic dystrophay presenting with ventilatory failure without significant limb weakness or any provocative challenge such as anesthesia or surgery. The PFT and polysomnographic findings support that this patient’s respiratory dysfunction was due to dual origin central and peripheral.