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Sei‐ichiro Motegi Yoko Yokoyama Akihiko Uchiyama Sachiko Ogino Yuko Takeuchi Kazuya Yamada Tomoyasu Hattori Hiroaki Hashizume Yuichi Ishikawa Makoto Goto Osamu Ishikawa 《The Journal of dermatology》2014,41(12):1047-1052
Atypical progeroid syndrome (APS), including atypical Werner syndrome (AWS), is a progeroid syndrome involving heterozygous mutations in the LMNA gene encoding the nuclear protein lamin A/C. We report the first Japanese case of APS/AWS with a LMNA mutation (p.D300N). A 53‐year‐old Japanese man had a history of recurrent severe cardiovascular diseases as well as brain infarction and hemorrhages. Although our APS/AWS patient had overlapping features with Werner syndrome (WS), such as high‐pitched voice, scleroderma, lipoatrophy and atherosclerosis, several cardinal features of WS, including short stature, premature graying/alopecia, cataract, bird‐like face, flat feet, hyperkeratosis on the soles and diabetes mellitus, were absent. In immunofluorescence staining and electron microscopic analyses of the patient's cultured fibroblasts, abnormal nuclear morphology, an increase in small aggregation of heterochromatin and a decrease in interchromatin granules in nuclei of fibroblasts were observed, suggesting that abnormal nuclear morphology and chromatin disorganization may be associated with the pathogenesis of APS/AWS. 相似文献
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Hany Goubran Botros Pierre Legrand Cecile Pagan Vincent Bondet Patrick Weber Mariem Ben‐Abdallah Nathalie Lemière Guillaume Huguet Jacques Bellalou Erik Maronde Pierre Beguin Ahmed Haouz William Shepard Thomas Bourgeron 《Journal of pineal research》2013,54(1):46-57
Abstract: Melatonin is a synchronizer of many physiological processes. Abnormal melatonin signaling is associated with human disorders related to sleep, metabolism, and neurodevelopment. Here, we present the X‐ray crystal structure of human N‐acetyl serotonin methyltransferase (ASMT), the last enzyme of the melatonin biosynthesis pathway. The polypeptide chain of ASMT consists of a C‐terminal domain, which is typical of other SAM‐dependent O‐methyltransferases, and an N‐terminal domain, which intertwines several helices with another monomer to form the physiologically active dimer. Using radioenzymology, we analyzed 20 nonsynonymous variants identified through the 1000 genomes project and in patients with neuropsychiatric disorders. We found that the majority of these mutations reduced or abolished ASMT activity including one relatively frequent polymorphism in the Han Chinese population (N17K, rs17149149). Overall, we estimate that the allelic frequency of ASMT deleterious mutations ranges from 0.66% in Europe to 2.97% in Asia. Mapping of the variants on to the 3‐dimensional structure clarifies why some are harmful and provides a structural basis for understanding melatonin deficiency in humans. 相似文献
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Systolic longitudinal strain correlates with visual assessment of regional left ventricular function during dobutamine stress echocardiography and discriminates the segments with induced contractility impairment 下载免费PDF全文
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