Körver-Keularts I M L W, de Visser M, Bakker H D, Wanders R J A, Vansenne F, Scholte H R, Dorland L, Nicolaes G A F, Spaapen L M J, Smeets H J M, Hendrickx A T M, van den Bosch B J C
Department of Clinical Genetics, Lab of Biochemical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands,
JIMD Rep. 2015;22:39-45. doi: 10.1007/8904_2015_409. Epub 2015 Mar 3.
In a 28-year-old male with a mild mitochondrial myopathy manifesting as exercise intolerance and early signs of cardiomyopathy without muscle weakness or ophthalmoplegia, we identified two novel mutations in the SLC25A4 gene: c.707G>C in exon 3 (p.(R236P)) and c.116_137del in exon 2 (p.(Q39Lfs*14)). Serum lactate levels at rest were elevated (12.7 mM). Both the patient's father and brother were heterozygous carriers of the c.707G>C mutation and were asymptomatic. The second mutation causes a 22 bp deletion leading to a frame shift likely giving rise to a premature stop codon and nonsense-mediated decay (NMD). The segregation of the mutations could not be tested directly as the mother had died before. However, indirect evidence from NMD experiments showed that the two mutations were situated on two different alleles in the patient. This case is unique compared to other previously reported patients with either progressive external ophthalmoplegia (PEO) or clear hypertrophic cardiomyopathy with exercise intolerance and/or muscle weakness carrying recessive mutations leading to a complete absence of the SLC25A4 protein. Most likely in our patient, although severely reduced, SLC25A4 is still partially present and functional.
在一名28岁男性患者中，其患有轻度线粒体肌病，表现为运动不耐受和心肌病的早期迹象，但无肌肉无力或眼肌麻痹。我们在SLC25A4基因中鉴定出两个新的突变：外显子3中的c.707G>C（p.(R236P)）和外显子2中的c.116_137del（p.(Q39Lfs*14)）。静息时血清乳酸水平升高（12.7 mM）。患者的父亲和兄弟均为c.707G>C突变的杂合携带者，且无症状。第二个突变导致22 bp的缺失，导致移码，可能产生过早的终止密码子和无义介导的衰变（NMD）。由于母亲已去世，无法直接检测突变的分离情况。然而，NMD实验的间接证据表明，患者的两个突变位于两个不同的等位基因上。与其他先前报道的患有进行性外眼肌麻痹（PEO）或明确的肥厚性心肌病且伴有运动不耐受和/或肌肉无力并携带导致SLC25A4蛋白完全缺失的隐性突变的患者相比，该病例具有独特性。在我们的患者中，SLC25A4虽然严重减少，但可能仍部分存在并具有功能。
