• Pediatric Infection and Vaccine
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• 제31권1호
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• pp.122-129
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• 2024

Chediak-Higashi syndrome (CHS) is a rare haematological and immunodeficiency disorder that occurs in childhood leading to recurrent infections, bleeding tendencies and progressive neurological dysfunction. Partial oculocutaneous albinism occurs in almost all cases. The exact prevalence is unknown, and the disease is caused by over 70 identified mutations in the lysosomal trafficking regulator gene. The presence of a bright polychromatic appearance from hair shaft and abnormally large intracytoplasmic granules, especially within neutrophils and platelets in the bone marrow is highly suggestive. Treatment is largely supportive, and the only curative treatment is through an allogeneic hematopoietic stem cell transplant. Without transplant, most patients will enter an accelerated phase of hemophagocytic lymphohistiocytosis (HLH) which carries a high mortality rate. We present a young male with CHS who we had followed through and eventually developed a fulminant accelerated phase. We believe this is only the second reported case of CHS in Malaysia.

• Radiation Oncology Journal
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• 제21권2호
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• pp.149-157
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• 2003

목적: 한국인 젊은 여성 유방암 환자에서 유방암 유전자 (BRCA)가 예후인자가 될 수 있는지 알아보기 위하여 본 연구를 시행하였다. 대상 및 방법: 대학병원에서 치료를 받은 환자 중에서 유방암이나 난소암의 가족력과 관계없이 40세 이하의 환자를 선택하였다. 환자의 나이는 18~40세이었고 중앙값은 34.5세이었다. 환자의 말초혈액에서 림프구를 모아 DNA를 추출하였으며 BRCA1과 BRCA2의 모든 염기 중에서 기능과 관계 있는 부위의 DNA를 직접염기서열 결정방식으로 검사하였다. 조직표본 검사가 가능한 환자는 면역화학조직검사를 시행하였다. 대상 및 방법: 60명의 환자 중에서 유방암 발생과 직접 관계가 있는 돌연변이가 11개(18.3%) 있었고(BRCA1 6명, BRCA2 5명), 의미를 알기가 곤란한 돌연변이가 7개 있었으며 반 수 이상의 돌연변이는 이제까지 보고되지 않은 것이었다. 그리고 대부분의 돌연변이 환자는 유방암이나 난소암의 가족력이 관찰되지 않았다. 유방암 유전자 돌연변이 환자는 한 명도 치료의 실패가 없었으며 한 면에서 반대측 유방암이 발생하였다. 7년 무병 생존율은 돌연변이 환자에서 50%, 돌연변이와 관계가 없는 환자에서 79%이었고 차이는 없었다. BRCA 관련 종양에서 에스트로젠, 프로제스테론 수용체 음성의 비율이 높았으며 조직학적 분화도가 낮았으나 예후는 비교대상에 비해 나쁘지 않았다. 결론: 한국의 젊은 여성 유방암 환자는 예후가 인자가 있어도 재발률이 낮았으며 유전자 돌연변이 이환율이 높았으나 암의 발현율은 상대적으로 낮은 것으로 추정되었다 이 결과를 확인하기 위해 더 많은 환자 집단과 오랜 추적기간의 연구가 필요하다.

• Asian-Australasian Journal of Animal Sciences
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• 제21권7호
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• pp.936-940
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• 2008

The PCR-amplified prion protein (PrP) gene was sequenced to determine the frequency of scrapie-associated as well as novel PrP genotypes in 72 healthy goats representing five breeds. A total of six genotypes were detected, resulting from the three reported 143 (H/R), 154 (R/H) and 240 (S/P) and the two novel 39 (S/R) and 185 (I/F) amino acid polymorphisms. Of the four silent mutations 42 (a$\rightarrow$g), 138 (c$\rightarrow$t), 231 (c$\rightarrow$a) and 237 (g$\rightarrow$c) detected in this study, 237 (g$\rightarrow$c) is novel. A genotype (SIP/RFP) harboring three amino acid polymorphisms 39 (S/R), 185 (I/F) and 240 (S/P) was found in few goats. Although both scrapie-associated genotypes with 143 (H/R) and 154 (R/H) polymorphisms and others with 39 (S/R), 185 (I/F) and 240 (S/P) polymorphisms were present in the studied Pakistani goats, their frequency was lower than that of the wild-type genotype SHRIS/SHRIS (34.7%). These results emphasize the need for further sequencing of the PrP gene in a large number of goats representing the five studied breeds, so that overall PrP variability can be assessed in these breeds in research addressing future concerns about scrapie.

• Asian Pacific Journal of Cancer Prevention
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• 제15권16호
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• pp.6685-6689
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• 2014

Background: Alterations in gene expression levels or mutations of tyrosine kinases are detected in some human cancers. In this study, we examined whether serine threonine tyrosine kinase 1 (STYK1)/novel oncogene with kinase domain (NOK) is overexpressed in patients with colorectal cancer. We also examined the clinical relevance of STYK1/NOK expression in cancer tissues. Materials and Methods: In tumor samples of patients with colorectal cancer and their matched non-cancerous samples, STYK1/NOK messenger RNA (mRNA) expression was analyzed by quantitative reverse transcriptase polymerase chain reaction. Associations between the expression levels of STYK1/NOK and clinicopathological characteristics of colorectal cancer were also assessed using Mann-Whitney U and Kruskal-Wallis tests. Results: Upregulation of STYK1/NOK was found in cancer tissues even at early stage of colorectal cancer compared to normal adjacent tissues. The optimal cutoff point of 0.198 the STYK1/NOK expression showed 0.78 sensitivity and 0.75 specificity for diagnosis. Overexpressed STYK1/NOK was correlated with tumor size but had no association with other clinicopathological characteristics of colorectal cancer. Conclusions: These results indicate that STYK1/NOK mRNA is widely expressed in the patients with colorectal cancer and suggest that inhibition of this molecule could potentially serve as a novel therapeutic target.

• Journal of Genetic Medicine
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• 제14권2호
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• pp.75-79
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• 2017

Duchenne and Becker muscular dystrophies (DMD and BMD, respectively) are X-linked neuromuscular disorders characterized by progressive muscle weakness and severe skeletal muscle degeneration. BMD is a milder form with a later onset. Patients with BMD tend to survive much longer than those with DMD. The differentiation between DMD and BMD is important in the genetic counseling of affected patients and their families. Since muscle biopsies are invasive procedures, the differential diagnosis of BMD and DMD is often dependent on the mutation identified in the DMD gene in affected patients. However, when a novel DMD mutation is identified, the differential diagnosis should be based on muscle biopsy findings with other clinical findings. Here we describe two Korean patients with BMD confirmed by muscle biopsy and genetic testing. Two novel exonic deletions in the DMD gene were identified.

• Asian Pacific Journal of Cancer Prevention
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• 제16권3호
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• pp.1247-1250
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• 2015

Background: Psoriasis, a common cutaneous disorder characterized by inflammation and abnormal epidermal proliferation with a prevalence of 2-3% in the general population, may be linked to certain types of cancer. Several studies have reported an association between interleukin 10 (IL-10) variant polymorphisms and inflammatory diseases such as psoriasis vulgaris although the results vary according to the population studied. No studies have been performed in the Saudi population. The present study concerned novel variants and other genetic polymorphisms of the promoter and exonic regions of the IL10 gene in patients with moderate to severe psoriasis and potential differences in genotype compared to a group of healthy volunteers. Materials and Methods: Patients with moderate to severe psoriasis and healthy controls with no personal or family history of psoriasis were selected from the central region of Saudi Arabia. Polymorphisms of the IL 10 gene of both groups were genotyped. Results: We observed two novel variants in 5'UTR region of the promoter precursor with higher prevalence of the genotype with both wild-type alleles in patients compared to the healthy control group. The differences at positions -377 and -150 were significantly associated with disease, both the variants conferred strong protection against psoriasis in Saudi patients. Conclusions: This observation provides further support for the importance of the part that IL10 plays in the pathophysiology of this disease. Confirmation of our findings in larger populations of different ethnicities would provide evidence for the role of IL-10 in psoriasis.

• Journal of Genetic Medicine
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• 제15권1호
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• pp.28-33
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• 2018

Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by the deficiency of ${\alpha}$-galactosidase A. Patients with classical FD present acroparesthesia, hypohidrosis, cornea verticillata, disseminated angiokeratoma, and microalbuminuria in childhood, and develop life-threatening renal, cardiac, and cerebrovascular complications typically after the fourth decade of life. To date, more than 700 mutations responsible for FD have been identified in the human GLA gene. Herein, we report a novel GLA mutation, c.1117_1141del25 (p.Gly373Profs*10), identified in an 11-year-old Korean boy with FD presenting early cardiac and neurologic manifestation and in other affected family members. The boy had acroparesthesia, hypohidrosis, cornea verticillata, and left ventricular hypertrophy. His mother and sister also had acroparesthesia. Two males on the mother's side had similar pain and died of unknown causes. The plasma ${\alpha}$-galactosidase A activity (4.1 nmol/hr/mg protein) of the patient was markedly lower than the mean value of the controls. The plasma level of globotriaosylsphingosine was elevated in the patient and all the carriers. We concluded the novel GLA mutation c.1117_1141del25 is a pathogenic mutation for FD, probably related to the early cardiac manifestation of FD.

• Clinical and Experimental Pediatrics
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• 제57권10호
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• pp.445-450
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• 2014

Purpose: Familial hypokalemic periodic paralysis (HOKPP) is an autosomal dominant channelopathy characterized by episodic attacks of muscle weakness and hypokalemia. Mutations in the calcium channel gene, CACNA1S, or the sodium channel gene, SCN4A, have been found to be responsible for HOKPP; however, the mechanism that causes hypokalemia remains to be determined. The aim of this study was to improve the understanding of this mechanism by investigating the expression of calcium-activated potassium ($K_{Ca}$) channel genes in HOKPP patients. Methods: We measured the intracellular calcium concentration with fura-2-acetoxymethyl ester in skeletal muscle cells of HOKPP patients and healthy individuals. We examined the mRNA and protein expression of KCa channel genes (KCNMA1, KCNN1, KCNN2, KCNN3, and KCNN4) in both cell types. Results: Patient cells exhibited higher cytosolic calcium levels than normal cells. Quantitative reverse transcription polymerase chain reaction analysis showed that the mRNA levels of the $K_{Ca}$ channel genes did not significantly differ between patient and normal cells. However, western blot analysis showed that protein levels of the KCNMA1 gene, which encodes $K_{Ca}$1.1 channels (also called big potassium channels), were significantly lower in the membrane fraction and higher in the cytosolic fraction of patient cells than normal cells. When patient cells were exposed to 50 mM potassium buffer, which was used to induce depolarization, the altered subcellular distribution of BK channels remained unchanged. Conclusion: These findings suggest a novel mechanism for the development of hypokalemia and paralysis in HOKPP and demonstrate a connection between disease-associated mutations in calcium/sodium channels and pathogenic changes in nonmutant potassium channels.

• Clinical and Experimental Pediatrics
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• 제48권3호
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• pp.337-341
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• 2005

선천성 갑상선 항진증은 드문 질환으로 모체로부터 TSH에 대한 자가항체가 태반을 통해 태아에게 전달되어 생기며 일시적인 경우가 많다. 선천성 갑상선 항진증이 지속되지만 자가면역질환의 검사 소견을 보이지 않을 때에는 TSHR의 돌연변이에 의한 갑상선 항진증을 고려해야 한다. 저자들은 TSHR의 돌연변이에 의한 갑상선 항진증 증례를 2례 경험하였기에 문헌고찰과 함께 보고하는 바이다.

• Neonatal Medicine
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• 제25권1호
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• pp.49-52
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• 2018

Arterial tortuosity syndrome (ATS) is a very rare autosomal recessive connective tissue disease characterized by generalized elongation and tortuosity of the medium- to large-sized arteries, and other systemic connective tissue manifestations. To date, this disease entity has not been reported in Korea. We report a case of ATS diagnosed in a neonate who presented with severe elongation and tortuosity of the aorta and its major branches, as well as the intracranial arteries. Additionally, the patient presented with a tortuous dilatation of the inferior vena cava, an aneurysmal dilatation of the extra-hepatic bile ducts, and an inguinal and sliding hiatal hernia. The diagnosis was confirmed using DNA sequencing analysis, and the patient demonstrated a compound heterozygosity for two novel mutations (c.738delG [p.Gln247Serfs*33] and c.362T>C [p.Ile121Thr]) in exon 2 of the SLC2A10 gene. Genetic analysis also confirmed that both parents were heterozygous carriers of the responsible mutations. Owing to such clinical manifestations, ATS is often misdiagnosed as other connective tissue diseases including Loeys-Dietz syndrome, Marfan syndrome, and Ehlers-Danlos syndrome. In patients presenting with a high index of suspicion, thorough clinical evaluation and screening for ATS including computed tomography or magnetic resonance angiography and target gene analysis are necessary for early diagnosis and management.