PDF(Pubmed)
Abstract：
The TRNT1 gene encodes tRNA nucleotidyltransferase 1, which catalyzes the addition of cytosine-cytosine-adenosine (CCA) to the ends of cytoplasmic and mitochondrial tRNAs. The most common clinical phenotype associated with TRNT1 is autosomal recessive sideroblastic anemia with B-cell immunodeficiency, periodic fever, and developmental delay (SIFD). Muscle involvement has rarely been reported in TRNT1-related disorders. Here we report a Chinese patient with incomplete SIFD and hyperCKemia, and explored the skeletal muscle pathological changes. The patient was a 3-year-old boy with sensorineural hearing loss, sideroblastic anemia, and developmental delay since infancy. At the age of 11 months, significantly increased levels of creatine kinase were noted, accompanied by mild muscle weakness. Whole-exome sequencing revealed compound heterozygous variants of the TRNT1 gene, c.443C > T (p.Ala148Val) and c.692C > G (p.Ala231Gly), in the patient. Western blot showed a decreased expression of TRNT1 and cytochrome c oxidase subunit IV (COX IV) in the skeletal muscle of the patient. Electron microscopy observation of skeletal muscle pathology revealed abnormal mitochondria of various sizes and shapes, supporting a diagnosis of mitochondrial myopathy. The present case indicates that in addition to the classic SIFD phenotype, TRNT1 mutations can cause mitochondrial myopathy, a rare clinical phenotype of TRNT1-related disorders.
摘要：
TRNT1基因编码tRNA核苷酸转移酶1,其催化胞嘧啶-胞嘧啶-腺苷(CCA)添加到胞质和线粒体tRNA的末端。与TRNT1相关的最常见的临床表型是常染色体隐性遗传铁粒幼细胞性贫血伴B细胞免疫缺陷,周期性发烧,和发育迟缓（SIFD）。在TRNT1相关疾病中很少报道肌肉受累。在这里，我们报告了一个中国患者的不完全SIFD和高CK血症，并探讨了骨骼肌的病理变化。病人是一个3岁的男孩，患有感音神经性听力损失，铁粒幼细胞性贫血,婴儿期以来的发育迟缓。在11个月大的时候，肌酸激酶水平显着升高，伴有轻度肌肉无力。全外显子组测序揭示了TRNT1基因的复合杂合变体，c.443C>T（p。Ala148Val）和c.692C>G（p。Ala231Gly),在病人身上。Westernblot显示患者骨骼肌中TRNT1和细胞色素c氧化酶亚基IV（COXIV）的表达降低。电镜观察骨骼肌病理显示线粒体有各种大小和形状的异常，支持线粒体肌病的诊断。目前的情况表明，除了经典的SIFD表型，TRNT1突变可引起线粒体肌病，TRNT1相关疾病的一种罕见临床表型。
