Two Novel Mutations in the SLC25A4 Gene in a Patient with Mitochondrial Myopathy
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.
KeywordsHypertrophic cardiomyopathy Mitochondrial myopathy Novel mutations SLC25A4
- Komaki H, Fukazawa T, Houzen H, Yoshida K, Nonaka I, Goto Y (2002) A novel D104G mutation in the adenine nucleotide translocator 1 gene in autosomal dominant progressive external ophthalmoplegia patients with mitochondrial DNA with multiple deletions. Ann Neurol 51:645–648PubMedCrossRefGoogle Scholar
- Neckelmann N, Li K, Wade RP, Shuster R, Wallace DC (1987) cDNA sequence of a human skeletal muscle ADP/ATP translocator: lack of a leader peptide, divergence from a fibroblast translocator cDNA, an coevolution with mitochondrial DNA genes. Proc Natl Acad Sci USA 84:7580–7584PubMedCentralPubMedCrossRefGoogle Scholar