Gene Found for Ghosal Hematodiaphyseal Dysplasia Syndrome: A Rare Syndrome with Increased Bone Density

A paper published online on Sunday in the journal Nature Genetics (abstract available here) describes the identification of mutations in a gene causing the rare, autosomal recessive, genetic syndrome Ghosal hematodiaphyseal dysplasia syndrome (GHDS).  GHDS is a disorder of increased bone density. 

The authors had previously mapped the disease gene to a segment of chromosome 7 by studying two families from Algeria and Tunisia.  In this study, they identified mutations in TBXAS1 - which encodes the enzyme thromboxane synthase - in the two original families, in addition to two other families from Tunisia and Pakistan with GHDS. 

Thromboxane synthase is one of the terminal enzymes in the arachidonic acid cascade and is involved in the production of thromboxane A2, which is known to be a powerful inducer of blood platelet aggregation in addition to having other physiologically important effects. 

The demonstration that TBXAS1 mutations cause GHDS, a disorder of increased bone density, suggests that thromboxane synthase and thromboxane A2 may play an important role in bone remodeling. 

Additionally, as is often the case with the identification of disease genes causing rare Mendelian (see "Mendelian trait" section of this article) syndromes, this paper suggests a candidate gene for a related, but much more common, condition; the involvement of TBXAS1 in a disorder of increased bone density suggests that it may be a candidate gene worth investigating in osteoporosis in the future.

Comments

[VWXYNot?]

I once saw an amazing conference presentation on this kind of "extreme geentics". The presenter used this example, and also that of a mutation in a novel pain receptor gene that caused members of one large family to feel absolutely no pain whatsoever. They were constantly breaking bones, burning themselves etc. The discovery of the gene initiated a research programme that aims to develop a new class of painkiller drugs that target the gene.

Really, really cool stuff.