ClinVar

Ultrastructural abnormalities seen in mitochondria of bone marrow cells of patients with myelodysplastic syndrome (MDS), such as pathologic iron accumulation in the mitochondria of erythroblasts, suggest that mitochondrial dysfunction may contribute to the pathophysiology of MDS. In a 65-year-old male patient with refractory anemia with excess blasts (RAEB), Gattermann et al. (2004) identified a novel somatic mutation of the mitochondrial MTTL1 gene, 3242G-A. Heteroduplex analysis indicated that 40 to 50% of mitochondrial DNA molecules in the bone marrow carried the mutation. The mutation was not detectable by heteroduplex analysis in the peripheral blood. However, peripheral blood CD34+ cells showed the mutation with a proportion of approximately 50%. In hematopoietic colony assays, CD34+ cells from bone marrow and peripheral blood yielded only colonies with wildtype mtDNA; this result indicated that the mtDNA mutation in CD34+ cells was associated with a maturation defect. Mitochondrial tRNA mutations impair mitochondrial protein synthesis, thereby causing dysfunction of the mitochondrial respiratory chain. Gattermann et al. (2004) suggested that this effect contributed to ineffective hematopoiesis in the patient.

Yakubovskaya et al. (2010) found that 3242G interacted with arg251 of MTERF1 (602318) and that the 3242G-A mutation profoundly reduced transcriptional termination by MTERF1.