• Asian Pacific Journal of Cancer Prevention
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• v.17 no.2
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• pp.603-608
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• 2016

Background: The investigation of mutation patterns in oncogenes potentially can make available a reliable mechanism for management and treatment decisions for patients with colorectal cancer (CRC). This study concerns the rate of KRAS and BRAF genes mutations in Iranian metastatic colorectal cancer (mCRC) patients, as well as associations of genotypes with clinicopathological features. Materials and Methods: A total of 1,000 mCRC specimens collected from 2008 to 2012 that referred to the Mehr Hospital and Partolab center, Tehran, Iran enrolled in this cross sectional study. Using HRM, Dxs Therascreen and Pyrosequencing methods, we analyzed the mutational status of KRAS and BRAF genes in these. Results: KRAS mutations were present in 33.6% cases (n=336). Of KRAS mutation positive cases, 85.1% were in codon 12 and 14.9% were in codon 13. The most frequent mutation at KRAS codon 12 was Gly12Asp; BRAF mutations were not found in any mCRC patients (n=242). In addition, we observed a strong correlation of KRAS mutations with some clinicopathological characteristics. Conclusions: KRAS mutations are frequent in mCRCs while presence of BRAF mutations in these patients is rare. Moreover, associations of KRAS genotypes with non-mucinous adenocarcinoma and depth of invasion (pT3) were remarkable.

• Journal of mucopolysaccharidosis and rare diseases
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• v.4 no.1
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• pp.14-20
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• 2018

Mucopolysaccharidoses (MPSs) are a group of rare inherited metabolic disorders caused by specific lysosomal enzyme deficiencies leading to the sequential degradation of glycosaminoglycans, causing substrate accumulation in various cells and tissues and progressive multiple organ dysfunction. The rare disease medical care team at Mackay Memorial Hospital in Taiwan has been dedicated to the study of MPSs for more than 20 years. Since 1999, more than 50 academic papers focusing on MPSs have been published in international medical journals. Topics of research include the following items regarding MPSs: incidence, natural history, clinical manifestations, gene mutation characteristics, cardiac function, bone mineral density, sleep studies, pulmonary function tests, hearing assessments, percutaneous endoscopic gastrostomy, anesthetic experience, imaging analysis, special biochemical tests, laboratory diagnostics, global expert consensus conferences, prenatal diagnosis, new drug clinical trials, newborn screening, and treatment outcomes. Of these published academic research papers, more than half were cross-domain, cross-industry, and international studies with results in cooperation with experts from European, American and other Asian countries. A cross-specialty collaboration platform was established based on high-risk population screening criteria with the acronym "BECARE" (Bone and joints, Eyes, Cardiac and central nervous system, Abdomen and appearance, Respiratory system, and Ear, nose, and throat involvement). Through this platform, orthopedic surgeons, rheumatologists, ophthalmologists, cardiologists, rehabilitation physicians, gastroenterologists, otorhinolaryngologists, and medical geneticists have been educated with regards to awareness of suspected cases of MPSs patients to allow for a further confirmative diagnosis of MPSs. Because of the progressive nature of the disease, an early diagnosis and early multidisciplinary therapeutic interventions including surgery, rehabilitation programs, symptom-based treatments, hematopoietic stem cell transplantation, and enzyme replacement therapy, are very important.

• Molecules and Cells
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• v.46 no.10
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• pp.579-588
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• 2023

Sarcomas are rare and heterogeneous mesenchymal neoplasms originating from the bone or soft tissues, which pose significant treatment challenges. The current standard treatment for sarcomas consists of surgical resection, often combined with chemo- and radiotherapy; however, local recurrence and metastasis remain significant concerns. Although immunotherapy has demonstrated promise in improving long-term survival rates for certain cancers, sarcomas are generally considered to be relatively less immunogenic than other tumors, presenting substantial challenges for effective immunotherapy. In this review, we examine the possible opportunities for sarcoma immunotherapy, noting cancer testis antigens expressed in sarcomas. We then cover the current status of immunotherapies in sarcomas, including progress in cancer vaccines, immune checkpoint inhibitors, and adoptive cellular therapy and their potential in combating these tumors. Furthermore, we discuss the limitations of immunotherapies in sarcomas, including a low tumor mutation burden and immunosuppressive tumor microenvironment, and explore potential strategies to tackle the immunosuppressive barriers in therapeutic interventions, shedding light on the development of effective and personalized treatments for sarcomas. Overall, this review provides a comprehensive overview of the current status and potential of immunotherapies in sarcoma treatment, highlighting the challenges and opportunities for developing effective therapies to improve the outcomes of patients with these rare malignancies.

• Journal of Interdisciplinary Genomics
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• v.6 no.1
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• pp.6-13
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• 2024

Background: ABO typing is crucial for ensuring safe blood transfusion and is commonly performed by examining antigen-antibody interactions. Determining ABO blood group can be difficult when dealing with ABO discrepancy and ABO subgroups. ABO genotyping may be necessary to resolve ABO discrepancy. ABO genotyping primarily involves direct sequencing, with the possibility of using other molecular methods. Methods: PCR and direct sequencing of exons 6 and 7 were performed for total 108 samples from June 2010 to December 2019. Also, other molecular methods including cloning sequencing and short tandem repeat analysis were carried out just in case. Sequencing data were compared with allele information of blood group antigen mutation databases. Results: The predominant causal allele among 108 ABO discrepant cases was cis-AB01, with 28 cases. This was followed by rare ABO alleles (B309, B306, A204, Bw29, and Ax01) with 14 cases, and blood chimera with 5 cases. Five new alleles were identified during the investigation. Conclusion: This study reaffirms that cis-AB is the most common cause of inherited ABO discrepancies, and cis-AB01 is the most prevalent cis-AB allele in the Korean population, also in the southeastern region. In addition, we discovered five new alleles and five blood chimeras by adopting sequencing analysis and additional molecular techniques to resolve ABO discrepancies, which provide regional data on rare alleles. This study presents rare and new ABO alleles and blood chimeras identified over a ten-year period at two major university hospitals in Southeastern Korea.

• Journal of mucopolysaccharidosis and rare diseases
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• v.3 no.1
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• pp.28-32
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• 2017

Lipoid congenital adrenal hyperplasia (LCAH) is the severe form of congenital adrenal hyperplasia and is characterized by adrenal insufficiency with hyperpigmentation and female external genitalia irrespective of genetic sex. The steroidogenic acute regulatory protein (StAR) is required for the transport of cholesterol into the mitochondria for steroidogenesis, and defects in the StAR gene account for the majority of LCAH cases. In this report, we present a two-day-old hyperpigmented infant with phenotypical female genitalia. With consideration of the clinical and laboratory findings, the infant was suspected of having adrenal insufficiency due to LCAH and treated with glucocorticoid, mineralocorticoid, and sodium chloride. Karyotyping revealed 46, XY. Upon pelvis ultrasonography, adrenal hyperplasia with abdominal masses (thought to be the testicles) was reported. Molecular analysis with targeted exome sequencing revealed the homozygote mutation of c.772C>T ($p.Q258^*$) in exon 7 of the StAR gene. The early detection and treatment of adrenal insufficiency in infants with hyperpigmentation can prevent clinically apparent adrenal crises. During follow-up, the patient had a good clinical condition and maintained normal electrolyte and adrenocorticotropic hormone levels with medication.

• Clinical and Experimental Pediatrics
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• v.59 no.11
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• pp.456-459
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• 2016

Triple-A syndrome, also known as Allgrove syndrome, is a rare autosomal recessive disorder. The 3 features of this syndrome are achalasia, adrenal insufficiency, and alacrima. Achalasia could be the first manifestation of the triple-A syndrome; however, its etiology is unclear. Alacrima is generally asymptomatic but can be detected by obtaining patient history. Although adrenal insufficiency could have manifestations such as asthenia, it might be wrongly diagnosed as muscle fatigue. Vitamin D and calcium supplements are usually prescribed for the prevention of osteoporosis. Neurologic manifestations could be present in adults. In some individuals with this disorder, genetic examination indicates mutations in both alleles of the AAAS gene, which encodes a special 546-amino-acid protein designated ALADIN, and in chromosome 12q13. The genetic cause of the triple A syndrome in some patients who do not have an identified mutation is unknown. While very few such cases have been reported till date, one such case was presented to us as an edentulous child.

• Neonatal Medicine
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• v.18 no.1
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• pp.143-147
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• 2011

Argininosuccinic aciduria (ASAuria) is a rare autosomal recessive urea cycle disorder. Neonatal presentation of ASAuria is the most common form. It is characterized by lethargy, feeding intolerance, decreased consciousness, and coma after 24 to 72 hours of birth. We describe a rare case of ASAuria in a female neonate who presented with severe hyperammonemia, a typical characteristic of urea cycle disorders. This patient's diagnosis was confirmed by biochemical analyses, and we found that the patient had a point mutation of the argininosuccinate lyase gene, which was homozygous for a novel 556C>T substitution. We have never seen the neonatal form of ASAuria in Korea. Therefore, this is the first report of neonatal onset ASAuria in Korea.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.14 no.1
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• pp.48-53
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• 2014

Smith-Lemli-Opitz syndrome (SLO) is a rare, autosomal recessive disease caused by an inborn error in cholesterol synthesis. Patients with this disease suffer from multiple malformations due to reduced activity of 7-dehydrocholesterol reductase (DHCR7), which increases 7-dehydrocholesterol (7DHC) and 8-dehydrocholesterol (8DHC) concentrations and decreases cholesterol concentration in body fluids and tissue. Here, we describe Korean siblings with SLO who were diagnosed recently, and performed a review of literature about Korean cases with SLO to date. Microcephaly and syndactyly of the second and third toes are the most common physical finding in SLOS patients. Other malformations including growth failure, cleft palate or bifid uvula, various heart malformation, genital ambiguity in males are also accompanied. Not all patients showed low levels of serum cholesterol, so DHCR7 mutation analysis can be helpful to confirmative diagnosis. Two mutations on p.R352 locus (p.R352W and p.R352Q) are commonly identified in Korean SLO patients. Although rare in Korea, SLO should be considered in the differential diagnosis of growth failure with intellectual disability, especially in patients with multiple congenital anomalies.

• Childhood Kidney Diseases
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• v.25 no.2
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• pp.128-132
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• 2021

Morning glory syndrome (MGS) is a rare congenital optic disc anomaly with a characteristic fundal finding with severe visual impairment. It may occur in association with various systemic manifestations, even though most of the reported cases were isolated. A 6-year-old male visited the nephrology clinic with a history of microscopic hematuria and at the age of 12 years, he was diagnosed thin glomerular basement membrane nephropathy by kidney biopsy. After the following years, the patient had progressive deterioration of visual acuity, and diagnosed as MGS. Whole Exome Sequencing of this patient and his mother revealed heterozygous COL4A4 mutations [c.81_86del (p.Ile29_Leu30del)]. It is more reasonable to consider MGS seen in this patient as a coincidental finding of autosomal dominant Alport syndrome. To our knowledge, this case represents the first case report of autosomal dominant Alport syndrome associated with MGS.

• Journal of Genetic Medicine
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• v.17 no.1
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• pp.43-46
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• 2020

The Shprintzen-Goldberg syndrome (SGS) is an extremely rare genetic disorder caused by heterozygous variant in SKI. SGS is characterized by neurodevelopmental impairment with skeletal anomaly. Recognition of SGS is sometimes quite challenging in practice because it has diverse clinical features involving skeletal, neurological, and cardiovascular system. Here we report a case of a 6-month-old boy who initially presented with developmental delay and marfanoid facial features including prominent forehead, hypertelorism, high arched palate and retrognathia. He showed motor developmental delay since birth and could not control his head at the time of first evaluation. His height was above 2 standard deviation score. Arachnodactyly, hypermobility of joints, skin laxity, and pectus excavatum were also noted. Sequencing for FBN1 was negative, however, a novel missense variant, c.350G>A in SKI was identified by sequential whole exome sequencing. To our knowledge, this is the first case with SGS with phenotypic features of SGS overlapping with those of the Marfan syndrome, diagnosed by next generation sequencing in Korea.