Kopajtich Robert, Murayama Kei, Janecke Andreas R, Haack Tobias B, Breuer Maximilian, Knisely A S, Harting Inga, Ohashi Toya, Okazaki Yasushi, Watanabe Daisaku, Tokuzawa Yoshimi, Kotzaeridou Urania, Kölker Stefan, Sauer Sven, Carl Matthias, Straub Simon, Entenmann Andreas, Gizewski Elke, Feichtinger René G, Mayr Johannes A, Lackner Karoline, Strom Tim M, Meitinger Thomas, Müller Thomas, Ohtake Akira, Hoffmann Georg F, Prokisch Holger, Staufner Christian
Institute of Human Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany; Institute of Human Genetics, Technische Universität München, 81675 Munich, Germany.
Department of Metabolism, Chiba Children's Hospital, Chiba 266-0007, Japan; Chiba Cancer Center Research Institute, Chiba 260-8717, Japan.
Am J Hum Genet. 2016 Aug 4;99(2):414-22. doi: 10.1016/j.ajhg.2016.05.027. Epub 2016 Jul 14.
tRNA synthetase deficiencies are a growing group of genetic diseases associated with tissue-specific, mostly neurological, phenotypes. In cattle, cytosolic isoleucyl-tRNA synthetase (IARS) missense mutations cause hereditary weak calf syndrome. Exome sequencing in three unrelated individuals with severe prenatal-onset growth retardation, intellectual disability, and muscular hypotonia revealed biallelic mutations in IARS. Studies in yeast confirmed the pathogenicity of identified mutations. Two of the individuals had infantile hepatopathy with fibrosis and steatosis, leading in one to liver failure in the course of infections. Zinc deficiency was present in all affected individuals and supplementation with zinc showed a beneficial effect on growth in one.
转运RNA合成酶缺陷是一类不断增加的遗传性疾病，与组织特异性（主要是神经方面）表型相关。在牛中，胞质异亮氨酰 - tRNA合成酶（IARS）错义突变会导致遗传性弱犊综合征。对三名患有严重产前生长发育迟缓、智力障碍和肌张力减退的无关个体进行外显子组测序，发现IARS存在双等位基因突变。酵母研究证实了所鉴定突变的致病性。其中两名个体患有伴有纤维化和脂肪变性的婴儿肝病，其中一人在感染过程中导致肝功能衰竭。所有受影响个体均存在锌缺乏，补充锌对其中一人的生长显示出有益效果。
