Identification of Maturity-Onset Diabetes of the Young Caused by Glucokinase Mutations Detected Using Whole-Exome Sequencing

Glucokinase maturity-onset diabetes of the young (GCK-MODY) represents a distinct subgroup of MODY that does not require hyperglycemia-lowering treatment and has very few diabetes-related complications. Three patients from two families who presented with clinical signs of GCK-MODY were evaluated. Whole-exome sequencing was performed and the effects of the identified mutations were assessed using bioinformatics tools, such as PolyPhen-2, SIFT, and in silico modeling. We identified two mutations: p.Leu30Pro and p.Ser383Leu. In silico analyses predicted that these mutations result in structural conformational changes, protein destabilization, and thermal instability. Our findings may inform future GCK-MODY diagnosis; furthermore, the two mutations detected in two Korean families with GCK-MODY improve our understanding of the genetic basis of the disease.

Expressional Subpopulation of Cancers Determined by G64, a Co-regulated Module

Studies of cancer heterogeneity have received considerable attention recently, because the presence or absence of resistant sub-clones may determine whether or not certain therapeutic treatments are effective. Previously, we have reported G64, a co-regulated gene module composed of 64 different genes, can differentiate tumor intra- or inter-subpopulations in lung adenocarcinomas (LADCs). Here, we investigated whether the G64 module genes were also expressed distinctively in different subpopulations of other cancers. RNA sequencing-based transcriptome data derived from 22 cancers, except LADC, were downloaded from The Cancer Genome Atlas (TCGA). Interestingly, the 22 cancers also expressed the G64 genes in a correlated manner, as observed previously in an LADC study. Considering that gene expression levels were continuous among different tumor samples, tumor subpopulations were investigated using extreme expressional ranges of G64-i.e., tumor subpopulation with the lowest 15% of G64 expression, tumor subpopulation with the highest 15% of G64 expression, and tumor subpopulation with intermediate expression. In each of the 22 cancers, we examined whether patient survival was different among the three different subgroups and found that G64 could differentiate tumor subpopulations in six other cancers, including sarcoma, kidney, brain, liver, and esophageal cancers.

Acute Tubulointerstitial Nephritis Induced by Deferasirox following Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia

Deferasirox is a once-daily, oral iron-chelating agent that is now widely available for the treatment of transfusional hemosiderosis. Deferasirox represents a significant advance in the treatment of iron overload, as the availability of an effective oral therapy has the potential to relieve many patients from the burden of frequent parenteral therapy with the previous reference standard iron chelator, deferoxamine. The well-known drug-related adverse events associated with deferasirox include gastrointestinal disturbances, rash, elevations in liver enzyme levels, and mild increases in serum creatinine levels, but acute renal failure is not common. The authors report a case of acute tubulointerstitial nephritis induced by deferasirox following hematopoietic stem cell transplantation for severe aplastic anemia

A Pilot Study of Comparisons Between 1999 and 2007 Data on Childhood Asthma Caregiver's Quality of Life Questionnaire / 소아알레르기및호흡기학회지

PURPOSE: Childhood asthma is one of the most frequent chronic inflammatory diseases of the respiratory tract and can have profound effects on emotional, and economical aspects not only for childhood asthma patients, but also the patient's caregivers. It was also performed has been done in Korea in 1999 under the supervision of The Korean Academy of Pediatric Allergy and Respiratory Disease (KAPARD). We compared and evaluated the data from the questionnaire between 1999 and 2007 in order to obtain the pilot data for a nation-wide study on the life quality of childhood asthma caregivers. METHODS: We selected childhood asthma patients at the Department of Pediatrics, Hanyang University Seoul Hospital and Guri Hospital. The contents and categories of the questionnaire were identical with the one developed by KAPARD, the questionnaire were filled up twice at first & second visit, divided into emotion and activity domains. All items were rated on a 5 scores from 1 to 5: 1, a lower quality of life; and 5, a satisfactory quality of life. For the validity of the study, the caregivers filled up the first and the second questionnaire at least at 1-week intervals the measurement of forced expiratory volume 1 (FEV1) at each time and also added an item in the second questionnaire which compared the difference between 2 visits, subsequently scoring +5 for the most improved state, -5 for the most aggravated state and 0 for the stationary state. RESULTS: In this study, may higher scores in the second visit suggested successful management of asthma may contribute to the improvement in the caregiver's quality of life. Particularly, items such as "Frustration", "Embarrassment", "Worry about daily works" and "Concern about side effect of medicine" have been improved in the emotion domain, and "sleepless", "Night awakening", and "Disturbance of housework" in the activity domain. Between 1999 and 2007, "Concerning", and "Concern about ordinary works" has been improved in the first visit, and "Disturbance of houseworks", "Worry about daily works" and "Concern about side effects of medicine" in the second visit. CONCLUSION: The results of this study suggest that there may be no significant different items regarding the quality of life between the stable and changed groups, suggesting that our questionnaire can be applicable to clinical practice.