• Journal of Genetic Medicine
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• v.18 no.1
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• pp.44-47
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• 2021

Cerebral creatine deficiency syndrome (CCDS) is a disorder where a defect is present in transport of creatine in the brain. Creatine plays an essential role in the energy metabolism of the brain. This is a genetic disorder, autosomal recessive or X linked, characterized by intellectual disability, speech and language delay, epilepsy, hypotonia, etc. Until recently very few number of cases have been reported. Here we report a case of 1.5-year-old boy who had epilepsy (epileptic spasm and generalized tonic clonic seizure), intellectual disability, microcephaly, hypotonia and speech delay. His magnetic resonance imaging of brain showed cortical atrophy and electroencephalography showed burst suppression pattern. The diagnosis was confirmed by clinical exome sequencing which showed novel mutation of SLC6A8+ in exon 9, suggestive of X linked recessive CCDS. The patient was then treated with glycine, L-arginine and creatine monohydrate with multiple antiepileptic drugs.

• Journal of Genetic Medicine
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• v.19 no.1
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• pp.38-41
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• 2022

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a single-gene disease caused by mutations in the neurogenic locus notch homolog protein 3 (NOTCH3) gene. The spectrum of clinical manifestations is broad, ranging from asymptomatic to typical ischemic stroke, and mainly depends on the location of the mutations. We describe the case of a 76-year-old female without apparent neurological deficits. However, brain magnetic resonance imaging revealed confluent lesions in the white matter. Direct sequencing of the NOTCH3 gene revealed a novel pathogenic mutation, c.811T>A, which results in a mild phenotype. Therefore, this report will expand the current knowledge in regards to the mutations that can cause CADASIL.

• Journal of Genetic Medicine
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• v.19 no.2
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• pp.100-104
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• 2022

The gene encoding solute carrier family 9 member 6 (SLC9A6) on Xq26.3 is associated with Christianson syndrome (CS) mimicking Angelman syndrome. In CS, developmental and epileptic encephalopathy (DEE) appears in about 20%, and DEE with spike-and-wave activation in sleep (SWAS) is reported only in several cases. A 10-year-old boy with DEE showed multidrug resistant focal seizures from 6 months of age. He had progressive microcephaly, regression, global developmental delay without speech, hyperkinesia, and truncal ataxia; he had a long thin face, esotropia, and happy demeanor. Brain magnetic resonance imaging demonstrated cerebellar atrophy. Electroencephalogram at 7.5 years of age showed nearly continuous diffuse paroxysms in slow wave sleep. The seizures were responsive to corticosteroids for a while. Trio whole exome sequencing exhibited a likely pathogenic variant of SLC9A6 in the proband and his asymptomatic mother: c.1194dup (p.Leu399AlafsTer12). This is a rare case report of CS with DEE-SWAS in a Korean patient.

• BMB Reports
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• v.42 no.10
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• pp.685-690
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• 2009

Angiogenesis is essential for tumor growth and vascular endothelial cell growth factor (VEGF) plays a key role in this process. Conversely, sphingosine 1-phosphate (S1P) is a biologically active sphingolipid known to play a key role in cancer progression by regulating endothelial cell proliferation and migration. In this study, the authors found that S1P increases the level of VEGF mRNA in human umbilical vein endothelial cells (HUVECs) and immortalized HUVECs (iHUVECs). Additionally, S1P was found to increase VEGF promoter activity in MS-1 mouse pancreatic islet endothelial cells. Furthermore, a pharmacological inhibitory study revealed that $G_{\alpha i/o}$-mediated phospholipase C, Akt, Erk, and p38 MAPK signaling are involved in this S1P-induced expression of VEGF. A component of AP1 transcription factor is important for S1P-induced VEGF expression. Taken together, these findings suggest that S1P enhances endothelial cell proliferation and migrat ion by upregulating the expression of VEGF mRNA.

• Journal of Korean Neurosurgical Society
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• v.59 no.5
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• pp.466-470
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• 2016

Objective : To determine imaging features that may separate adamantinomatous and papillary variants of craniopharyngiomas given that tumors with adamantinomatous signature features are associated with higher recurrence rates, morbidity, and mortality. We specifically reviewed calcification on CT, T1 bright signal intensity, and cystic change on T2 weighted images for differentiating these two types. Methods : We retrospectively reviewed the MRI and CT studies in 38 consecutive patients with pathologically proven craniopharyngiomas between January 2004 and February 2014 for the presence of calcification on CT scans, bright signal intensity on T1 weighted images, and cystic change on T2 weighted images. Results : Of the 38 craniopharyngiomas, 30 were adamantinomatous type and 8 were papillary type. On CT scans, calcification was present in 25 of 38 tumors. All calcified tumors were adamantinomatous type. Twenty four of 38 tumors had bright signal intensity on T1 weighted images. Of these 24 tumors, 22 (91.7%) were adamantinomatous and 2 were papillary type. Cystic change on T2 weighted images was noted in 37 of 38 tumors; only 1 tumor with papillary type did not show cystic change. Conclusion : T1 bright signal intensity and calcification on CT scans uniformly favor the adamantinomatous type over papillary type of craniopharyngioma in children. However, these findings are more variable in adults where calcification and T1 bright signal intensity occur in 70.6% and 58.8% respectively of adult adamantinomatous types of craniopharyngiomas.

• Journal of Genetic Medicine
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• v.9 no.2
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• pp.84-88
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• 2012

Purpose: Neurofibromatosis type 1 (NF1), which is caused by mutations of the NF1 gene, is the most frequent single gene disorder to affect the nervous system. Unidentified bright objects (UBOs) are commonly observed on brain magnetic resonance imaging (MRI) in patients with NF1. However, their clinical and pathologic significance is not well understood. The purpose of this study was to investigate the correlation between UBOs and cerebral glucose metabolism measured by $^{18}F$-2-Fluoro-2-deoxy-D-glucose ($^{18}F$-FDG) positron emission tomography (PET) in Korean patients with NF1. Materials and Methods: Medical records of 75 patients (34 males and 41 females) with NF1 who underwent brain MRI and PET between 2005 and 2011 were evaluated retrospectively. Clinical data including demographics, neurological symptoms, and brain MRI and PET findings, were reviewed. Results: UBOs were detected in the brain MRI scans of 31 patients (41%). The region most frequently affected by UBOs was the basal ganglia. The most frequent brain PET finding was thalamic glucose hypometabolism (45/75, 60%). Of the 31 patients with UBOs, 26 had thalamic glucose hypometabolism on brain PET, but the other 5 had normal brain PET findings. Conversely, of the 45 patients with thalamic glucose hypometabolism on brain PET, 26 showed UBOs on their brain MRI scans, but 19 had normal findings on brain MRI scans. Conclusion: UBOs on brain MRI scans and thalamic glucose hypometabolism on PET appear to be 2 distinctive features of NF1 rather than correlated symptoms. Because the clinical significance of these abnormal imaging findings remains unclear, a longitudinal follow-up study of changes in clinical manifestations and imaging findings is necessary.

• Journal of Genetic Medicine
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• v.10 no.2
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• pp.88-93
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• 2013

Alexander disease (ALXD) is a rare demyelinating disease of the white matter of the brain that is caused by a mutation in the glial fibrillary acidic protein (GFAP) gene. The overexpression of GFAP in astrocytes induces a failure in the developmental growth of the myelin sheath. The neurodegenerative destruction of the myelin sheath of the white matter is accompanied by an accumulation of abnormal deposits of Rosenthal fibers in astrocytes, which is the hallmark of ALXD. The disease can be divided into four groups based on the onset age of the patients: neonatal, infantile, juvenile, or adult. Early-onset disease is more severe, progresses rapidly, and results in a shorter life span than late-onset cases. Magnetic resonance imaging and genetic tests are mostly used for diagnostic purposes. Pathological tests of brain tissue for Rosenthal fibers are definitive diagnostic methods. Therapeutic strategies are being investigated. Ceftriaxone, which is an enhancer of glial glutamate transporter (GLT-1) expression, is currently in clinical trials for the treatment of patients with ALXD. To date, there are no clinically available treatments. The cause, pathology, pathophysiology, inheritance, clinical features, diagnosis, and treatment of ALXD will be reviewed comprehensively.

• Journal of Genetic Medicine
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• v.3 no.1
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• pp.1-4
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• 1999

Scimitar syndrome is a rare congenital anomaly that is characterized by hypoplasia of the right lung and the right pulmonary artery with anomalous pulmonary venous drainage to the inferior vena cava. The scimitar vein is usually visible on chest radiographs, but may be obscured by the heart. It is essential for surgical correction to establish the point of drainage of the anomalous vein and associated anomalies. There are recent reports of familial total anomalous pulmonary venous return suggesting heritable forms of this anomaly. Although genetic factors are believed to have important roles in congenital heart disease, few genes involved in heart development have been located. We report a case of familial chromosome 9 inversion with Scimitar syndrome in an offspring who presented with dextrocardia. Evaluation with magnetic resonance cineangiograph imaging demonstrated an anomalous pulmonary vein draining into the inferior vena cava above the diaphragm and hypoplasia of the right lung and the right pulmonary artery. Chromsome analysis showed pericentric inversion of chromosome 9, inv 9 (p13, q21), in the patient and his mother as well. A brief review of the related literature is also included.

• Journal of Genetic Medicine
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• v.11 no.2
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• pp.83-85
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• 2014

Dural ectasia refers to the widening or ballooning of the dural sac surrounding the spinal cord. It can affect any plane of the spinal canal, but occurs primarily in the lumbosacral region. Dural ectasia is present in 63-92% patients who have Marfan syndrome, and is related to Ehlers-Danlos syndrome, neurofibromatosis type I, and ankylosing spondylitis. The most common symptoms are low back pain, headache, weakness, numbness above and below the affected limb, and occasional rectal and genital pain. However, in most patients, dural ectasia is usually asymptomatic. We report the case of a 5-year-old boy who presented with a severe headache who had been diagnosed with Marfan syndrome. During the evaluation, magnetic resonance imaging of the lumbar and sacral spine revealed dural ectasia. To our knowledge, this is the first report on Marfan syndrome with symptomatic dural ectasia in Korea. We concluded that dural ectasia should be suspected in patients diagnosed with Marfan syndrome who have a severe headache.

• Journal of Genetic Medicine
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• v.16 no.1
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• pp.43-47
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• 2019

Ehlers-Danlos syndrome (EDS) VIII is an autosomal dominant inherited connective tissue disorder characterized by intractable periodontal inflammation, absence of gingiva, pretibial plaques, skin hyperextensibility, joint hypermobility, and tissue fragility with onset in the childhood or adolescence. In a recent report, heterozygous variants of the C1R or C1S related to the classical complement pathway were identified in families with history of EDS VIII. The current report describes a Korean 34-year-old female carrying a novel missense variant of C1R c.925T>G (p.Cys309Gly) and exhibiting early severe periodontitis, skin fragility, and joint hypermobility. The patient also had frontal, parietal, and temporal white matter brain lesions without definite vascular abnormalities on brain magnetic resonance imaging, which have not been surveyed meticulously in EDS VIII. Considering the genetic alteration of classic complement pathways in this condition, it is necessary to carefully observe multisystemic inflammation processes such as changes in brain white matter.