Genetics of Down Syndrome: An Update

Since the discovery of the chromosomal basis of Down syndrome (DS) in 1959, researches are still trying to understand the genetic basis of this particular unique common disorder that cannot be simply explained by an additional chromosome 21. Recent advances in molecular genetics had shed the light on several genes peculiar to this disorder like DYRK1A involved in cognitive dysfunctions and GATA1 involved in transient myeloproliferative disease. Some of these genes are actually beneficial when found in excess like COL18A1 which encodes endostatin, a potent angiogenesis inhibitor that inhibit the progression of solid tissue tumors and thus may have a potential therapeutic effect as anticancer therapy, as an anti-inflammatory agent and for protection against diabetic retinopathy. Gene therapy - or better to say chromosome therapy - for patients with DS is a recent break through where scientists were able to silence the extra chromosome and reverse the neuron proliferation dysfunction. This will not only help patients with DS but could be applied to all chromosomal trisomies. By understanding the pathogenetic mechanisms of DS, the near future is holding hope not only for treatment of DS cognitive dysfunction but also cures for solid tumours and certain disorders that will be done through inducing trisomy 21 in affected cells!

Keywords: AIRE, Blessing effect, Chromosomes, Cytogenetics, Down syndrome, DSCR-1, DYRK1A, Endostatin, GATA1, Gene therapy, JAK2, Lucky mothers, Molecular, Mosaicism, Nondisjunction, Overexpression, Polymorphism, Robertsonian translocation, TAM, Trisomy 21.