Myelodysplastic syndrome (MDS) is a highly heterogeneous disease. The etiology involves both environmental and genetic factors. Identification of new pathogenetic mechanisms may have important impact on the choice of treatment as well as the development of new treatment options. Familial disease gives a unique opportunity to study those mechanisms. Familial occurrence of MDS is rare and mainly associated with autosomal recessive genetic syndromes such as Fanconi anaemia, Bloom syndrome, Diamond-Blackfan syndrome and megakaryocytic thrombocytopenia. Cytogenetic abnormalities are in general seen in 50% of MDS cases. Most frequently, abnormalities involving chromosome 5 or 7 are observed, which has also been described in rare cases of familial MDS. We here present a unique family in which a father and two of his three children were diagnosed with refractory anemia (RA) with cytogenetic aberrations resulting in three different translocations involving chromosome 1q and resulting in trisomy of 1q. Trisomy 1q is often seen in sporadic MDS, but the unbalanced translocations observed in this family may originate from inherited centromere instability of chromosome 1. The genetic background for the observed centromere instability could be a DNA methylation deficiency, which we plan to investigate further.

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