The work reports the identification on chromosome 13, of a gene - GPC6 – that is shown to be crucial to normal bone development. The research will allow a better comprehension, as well as prevention, of the disease, by permitting, for example, the screening of potential mutation carriers for pregnancy advise.
However, and most importantly, it will also help to understand better bone development and its molecular bases. Recessive omodysplasia is characterised by deficient bone growth, more marked at the long bones of the limbs – humerus and femur-resulting in short-limbed dwarfism, with adults measuring from 132 to 144 centimetres. Other abnormalities include forearms dislocation, facial dysmorphy, as well as occasional heart defects and cognitive delays.
Until now not much was known about its origin except for the fact that it had a genetic cause – as it was passed between generations of a family – and that was a recessive disease. Recessive diseases are those where both copies of the affected gene need to be abnormal for the disorder to manifest itself (humans, like most animals and plants, have two copies of every gene in their genome, one inherited from each parent) what in practice means that for a child to be sick both parents’ families have to be affected.
With this information researchers decided to study nine patients and their families using a technique called genome-wide linkage scan to try to locate and then identify the mutated gene behind the disorder. By using multiple markers throughout the entire genome Campos-Xavier and colleagues were able to pinpoint the responsible gene to chromosome 13 on a region containing about 15 genes, which then needed to be analysed individually.
In conclusion, Belinda Campos-Xavier and colleagues found that recessive omodysplasia is caused by a non-functional GPC6 protein probably by leading to the disruption of growth-factor signals – GPCs are known to promote the association of growth factors with their receptors - compromising long-bone formation.
MEDICA.de; Source: The American Journal of Human Genetics