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.
