Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
Mitochondrion. 2013 Nov;13(6):743-8. doi: 10.1016/j.mito.2013.03.002. Epub 2013 Mar 14.
Exome sequencing identified compound heterozygous mutations in the recently discovered mitochondrial methionyl-tRNA formyltransferase (MTFMT) gene in two sisters with mild Leigh syndrome and combined respiratory chain deficiency. The mutations lead to undetectable levels of the MTFMT protein. Blue native polyacrylamide gel electrophoresis showed decreased complexes I and IV, and additional products stained with complex V antibodies, however the overall steady state level of mt-tRNA(Met) was normal. Our data illustrate that exome sequencing is an excellent diagnostic tool, and its value in clinical medicine is enormous, however it can only be optimally exploited if combined with detailed phenotyping and functional studies.
外显子组测序在两位患有轻度 Leigh 综合征和呼吸链复合缺陷的姐妹中发现了最近发现的线粒体甲硫氨酰-tRNA 甲酰基转移酶（MTFMT）基因的复合杂合突变。这些突变导致 MTFMT 蛋白水平无法检测到。蓝色非变性聚丙烯酰胺凝胶电泳显示复合物 I 和 IV 减少，并用复合物 V 抗体染色的其他产物，但 mt-tRNA（Met）的整体稳态水平正常。我们的数据表明，外显子组测序是一种出色的诊断工具，其在临床医学中的价值巨大，但是如果与详细的表型和功能研究相结合，它才能得到最佳利用。
