Genet Test Mol Biomarkers 2010 Dec 12;14(6):793-6. Epub 2010 Oct 12.
Genomic Unit for the Diagnosis of Human Pathologies, Center for Genomics, Bioinformatics, and Biostatistics, San Raffaele Scientific Institute, Milan, Italy.
The storage of iron in the cells is mainly accomplished by cytosolic ferritins. The perturbation of ferritin function may result in accumulation of excess iron in cells and tissues and increased oxidative stress, common features of different genetic and acquired disorders. Mutations in L-ferritin have been associated with neuroferritinopathy, a rare and severe movement disorder with abnormal brain iron storage. Recently, a novel form of ferritin has been discovered, which localizes in the mitochondrial matrix and plays an important role in iron homeostasis in these organelles. The possible association of sequence variations in the mitochondrial ferritin (FtMt) gene with disorders with aberrant iron distribution has not been investigated yet. We set up a denaturing high-performance liquid chromatography (DHPLC)-based screening for FtMt and analyzed the genomic DNA of patients with myelodysplastic syndromes (# 63) or with Parkinson's disease (# 332) and other movement disorders such as pantothenate kinase-associated neurodegeneration (# 7), restless legs syndrome (# 23), and suspected neuroferritinopathy (# 7) and of control subjects (# 342). We detected eight different types of substitution, all at the heterozygous state. Six of them caused amino acid changes, but none of them was predicted to drastically perturb FtMt structure and/or function. The c + 134C > A (P45H) variation, which was the most common (# 28), was less represented in the Parkinson's population, although not significantly (p = 0.07). The analysis suggests that sequence variations in the coding region of FtMt are not involved in the development of myelodysplastic syndromes and Parkinson's disease.