PubMed · 12681354
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Richard D Brunning. 2003. MDS--new classification, new problem?. https://doi.org/10.1016/s0145-2126(02)00302-8
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The hunt for pathogenic mitochondrial DNA (mtDNA) mutations is often fueled by the seeming novelty of mutations that are either nonsynonymous or affect the protein synthesis machinery in patients. In order to determine the novelty of a detected mutation, the working geneticist nearly always consults MITOMAP--often exclusively. By reanalyzing some case studies of refractory anemia with ring sideroblasts, prostate cancer, and hearing impairment, we demonstrate that the practice of solely relying on MITOMAP can be most misleading. A notorious example is the T1243C mutation, which was assessed to be novel and deemed to be associated with some (rare) disease simply because researchers did not realize that T1243C defines a deep branch in the Eurasian mtDNA phylogeny. The majority of 'novel' mutations suspected of being pathogenic are in actual fact known (and presumably neutral) polymorphisms (although unknown to MITOMAP), and this becomes glaringly evident when proper database searches and straightforward Internet queries are carried out.
Deletions of 5q in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are of different extents and the majority map to sub-bands 5q13.3 and 5q33.1. To further pinpoint these deletions, we have performed a detailed interphase fluorescence in situ hybridization (I-FISH) analysis with precisely mapped BAC probes. Eleven MDS and two AML patients with a sole cytogenetically visible del(5q) were studied. The proximal deletion endpoints were localized between 75 and 86 megabases (Mb) (5q13, five times), 86 and 96 Mb (5q14 approximately q15, four times), and at various sites in the other four. The distal breakpoints mapped between 153 and 155 Mb (5q33.2, five times), 156 and 158 Mb (5q33.3, three times), 158 and 164 Mb (5q34, two times), and 164 and 181 Mb (telomere) in three. The largest deletion was approximately 70 Mb and the smallest was 43 Mb. These studies show that cytogenetically similar appearing deletions in 5q are highly variable in molecular terms. We also found that in MDS cases with a blast count between 0 and 13%, cells with a del(5q) were present in 24-90% of interphase (nondividing) cells and in 30-100% of metaphase (dividing) cells. In the two AML patients with a blast count of 30 and 80%, del(5q) was found in 35 and 95% interphase cells and 95 and 100% of metaphase cells, respectively. This demonstrates that a low blast count can be associated with a high proportion of 5q- cells in the bone marrow.
A small number of cases of Crohn disease associated with myelodysplastic syndromes or leukemia have been reported in adults in the last 25 years in the English-language medical literature. The authors report a case of a 9-year-old boy who developed Crohn disease and myelodysplastic syndrome concurrently. Analysis of his bone marrow showed a chromosome 20 abnormality. Although chromosome 20 abnormalities have been reported in a minority of these patients, the significance of this association remains unclear at the present time.