• Journal of Genetic Medicine
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• v.20 no.2
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• pp.31-38
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• 2023

Rare diseases, even though defined as fewer than 20,000 in South Korea, with over 8,000 rare Mendelian disorders having been identified, they collectively impact 6-8% of the global population. Many of the rare diseases pose significant challenges to patients, patients' families, and the healthcare system. The diagnostic journey for rare disease patients is often lengthy and arduous, hampered by the genetic diversity and phenotypic complexity of these conditions. With the advent of next-generation sequencing technology and clinical implementation of exome sequencing (ES) and genome sequencing (GS), the diagnostic rate for rare diseases is 25-50% depending on the disease category. It is also allowing more rapid new gene-disease association discovery and equipping us to practice precision medicine by offering tailored medical management plans, early intervention, family planning options. However, a substantial number of patients remain undiagnosed, and it could be due to several factors. Some may not have genetic disorders. Some may have disease-causing variants that are not detectable or interpretable by ES and GS. It's also possible that some patient might have a disease-causing variant in a gene that hasn't yet been linked to a disease. For patients who remain undiagnosed, reanalysis of existing data has shown promises in providing new molecular diagnoses achieved by new gene-disease associations, new variant discovery, and variant reclassification, leading to a 5-10% increase in the diagnostic rate. More advanced approach such as long-read sequencing, transcriptome sequencing and integration of multi-omics data may provide potential values in uncovering elusive genetic causes.

• Journal of mucopolysaccharidosis and rare diseases
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• v.4 no.1
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• pp.7-10
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• 2018

Rare diseases are life threatening or chronically debilitating diseases with a low prevalence (less than 2,000 people in a population), which includes lysosomal storage diseases. These diseases are often seen as unimportant especially in developing countries, such as Indonesia, due to small number of patients. National Rare Disease Center in Indonesia was pioneered almost 20 years ago and officially established in 2017 by the Indonesian Minister of Health. Lysosomal storage disease become the most commonly found inborn errors of metabolism (IEM) in Indonesia due to easily accessible diagnostic facilities. Currently there are 7 patients receiving ERT in this mixed-donation scheme, one patient with Gaucher disease and 6 patients with MPS type II. Few challenges for ERT in Indonesia include importation through special access scheme, preparation of ERT infusion in intensive care settting, and cost of treatment. Even with limited resources, healthcare professionals in Indonesia have been giving the best care possible for rare disease patients, especially to provide diagnostic facilities through collaboration and treatment options for treatable rare diseases. Improvements in care for rare disease patients are still needed.

• Research in Community and Public Health Nursing
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• v.17 no.3
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• pp.364-375
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• 2006

Purpose: The purpose of the study was to investigate burden and the qualify of life in caregivers who are taking care of home-based rare and incurable disease patients. Methods: The subjects of this study were 300 caregivers of rare and incurable disease patients registered at five health centers in Seoul. A survey was conducted by mail and visit in person during the period from the 25th of March to the 12th of May 2005. Collected data were analyzed through t-test, ANOVA, Pearson's correlation coefficient. Result: The mean burden of caregivers was 3.42, and the mean qualify of life of caregivers was 2.71. Burden and QoL showed significant differences according to caregivers' characteristics such as sender, age, relation to the patient, academic qualification, religion, occupation, monthly household income and perceived health condition. Caregivers' burden was in an inverse correlation with their quality of life. Conclusions: According to the results of this study, rare and incurable disease caregivers' burden and their quality of life were in a significant correlation with each other. In order to improve caregivers' quality of life by reducing their burden, we need to reestablish comprehensive policies for rare and incurable disease management including nursing intervention strategies for caregivers.

• Journal of Genetic Medicine
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• v.20 no.1
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• pp.1-5
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• 2023

Until now, rare disease studies have mainly been carried out by detecting simple variants such as single nucleotide substitutions and short insertions and deletions in protein-coding regions of disease-associated gene panels using diagnostic next-generation sequencing in association with patient phenotypes. However, several recent studies reported that the detection rate hardly exceeds 50% even when whole-exome sequencing is applied. Therefore, the necessity of introducing whole-genome sequencing is emerging to discover more diverse genomic variants and examine their association with rare diseases. When no diagnosis is provided by whole-genome sequencing, additional omics techniques such as RNA-seq also can be considered to further interrogate causal variants. This paper will introduce a description of these multi-omics techniques and their applications in rare disease studies.

• Genomics & Informatics
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• v.19 no.3
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• pp.28.1-28.4
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• 2021

Since only a small number of patients have a rare disease, it is difficult to identify all of the features of these diseases. This is especially true for patients uncommonly presenting with rare diseases. It can also be difficult for the patient, their families, and even clinicians to know which one of a number of disease phenotypes the patient is exhibiting. To address this issue, during Biomedical Linked Annotation Hackathon 7 (BLAH7), we tried to extract Alexander disease patient data in Portable Document Format. We then visualized the phenotypic diversity of those Alexander disease patients with uncommon presentations. This led to us identifying several issues that we need to overcome in our future work.

• Biomolecules & Therapeutics
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• v.31 no.2
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• pp.219-226
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• 2023

Furanocoumarin 8-methoxypsoralen (8-MOP) is the parent compound that naturally occurs in traditional medicinal plants used historically. 8-MOP has been employed as a photochemotherapeutic component of Psoralen + Ultraviolet A (PUVA) therapy for the treatment of vitiligo and psoriasis. Although the role of 8-MOP in PUVA therapy has been studied, little is known about the effects of 8-MOP alone on human gastric cancer cells. In this study, we observed anti-proliferative effect of 8-MOP in several human cancer cell lines. Among these, the human gastric cancer cell line SNU1 is the most sensitive to 8-MOP. 8-MOP treated SNU1 cells showed G1-arrest by upregulating p53 and apoptosis by activating caspase-3 in a dose-dependent manner, which was confirmed by loss-of-function analysis through the knockdown of p53-siRNA and inhibition of apoptosis by Z-VAD-FMK. Moreover, 8-MOP-induced apoptosis is not associated with autophagy or necrosis. The signaling pathway responsible for the effect of 8-MOP on SNU1 cells was confirmed to be related to phosphorylated PI3K, ERK2, and STAT3. In contrast, 8-MOP treatment decreased the expression of the typical metastasis-related proteins MMP-2, MMP-9, and Snail in a p53-independent manner. In accordance with the serendipitous findings, treatment with 8-MOP decreased the wound healing, migration, and invasion ability of cells in a dose-dependent manner. In addition, combination treatment with 8-MOP and gemcitabine was effective at the lowest concentrations. Overall, our findings indicate that oral 8-MOP has the potential to treat early human gastric cancer, with fewer side effects.

• Journal of Chest Surgery
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• v.27 no.5
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• pp.402-406
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• 1994

Behcet`s disease is a rare systemic disease of unknown cause and it is a progressive disorder with episodes of activity and remission. The major features are oral and genital ulceration and skin and eye lesions. Pulmonary involvement is rare, and we have experienced a 38 year old female patient who had undergone right lower lobe lobectomy due to extensive, rapidly growing pulmonary thromboemboli and pseudoaneurysm in pulmonary artery.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.22 no.4
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• pp.392-399
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• 2019

Wilson disease a rare autosomal recessive inherited disorder of copper metabolism, is characterized by excessive deposition of copper in the liver, brain, and other tissues. Wilson disease is often fatal if it is not recognized early and treated when it is symptomatic. Gitelman syndrome is also an autosomal recessive kidney disorder characterized by low blood levels of potassium and magnesium, decreased excretion of calcium in the urine, and elevated blood pH. Hereditary sensory autonomic neuropathy type IV (HSAN-IV), a very rare condition that presents in infancy, is characterized by anhidrosis, absence of pain sensation, and self-mutilation. It is usually accompanied by developmental delay and mental retardation. We report a case of Wilson disease manifested as fulminant hepatitis, acute pancreatitis, and acute kidney injury in a 15-year-old boy comorbid with HSAN-IV and Gitelman syndrome. Such concurrence of three genetic diseases is an extremely rare case.

• Korean Journal of Clinical Pharmacy
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• v.16 no.2
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• pp.107-112
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• 2006

This study was aimed to investigate the current status and expectations of orphan drugs in Korea. The Korea Orphan Drug Center was established to supply many medicines for the patients with rare diseases. Among the medicines supplied by the Center, the number designated as the orphan drugs by the KFDA is quite few. However, a few of medicines are not under circulation even if the items are designated as the orphan drugs. Neoplasm-related medicines, infectious and parasitic disease-related medicines, endocrine, nutritional and metabolic disease-related medicines are the ones circulated most. There are several unapproved drugs among the medicines supplied by the Center. It's because the director of the Center can import the goods without a process to getting an approval from the KFDA. The Korea Orphan Drug Center has contributed to the selection of the medicines for treating the rare disease. On the contrary, some problems remain in the supply process. The safety and effectiveness of the medicines supplied by the Center are not guaranteed. So far, rare diseases have no specific legal definition, and therefore are only referred to in terms of the population of patients, which prevent from establishing the range of medicines. The introduction of Special Access Program or Access to Unapproved Therapeutic Goods will be the solution of these problems. In addition, it is another solution to keep intimate relations with the Rare and Intractable Disease Center and the Medicine Safety Information Center which will be open soon.

• Communications for Statistical Applications and Methods
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• v.11 no.1
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• pp.181-187
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• 2004

One of objectives in epidemiologic studies is to detect the amount of change caused by a specific risk factor. Risk ratio is one of the most useful measurements in epidemiology. When we perform the inference for this measurement with rare events, the standard approach based on the normal approximation may fail, in particular when there are no disease cases observed. In this paper, we discuss and evaluate several existing methods for constructing a confidence interval of risk ratio through simulation when the disease of interest is a rare event. The results in this paper provide guidance with how to construct interval estimates for risk difference and risk ratio when there are no disease cases observed.