Genetic cause of hypertrichosis

Congenital generalized hypertrichosis (CGH) is an extremely rare condition of excessive hair growth.  You may know it as the somewhat pejorative ‘werewolf syndrome’. Long thought to be a genetic disorder, it has only recently been traced to an insertion in a specific region of the X chromosome.

A team of researchers from the University of Southern California and from various Chinese institutes was able to compare two families, one Mexican and one Chinese, with histories of CGH.  The Chinese family members who suffered from CGH had an insertion of a piece of chromosome 5 into region q27.1 of an X chromosome.  That means that at some time in the past, a chunk of chromosome 5 had broken off from its usual position.  Rather than being stitched back together in the right place back on chromosome 5, the DNA repair mechanisms had stuck the chunk near the tip of the X chromosome.  This event had occurred in a stem cell (egg or sperm) and consequently was passed on to future generations.

At this point, it wasn’t clear whether the problem was in the disruption of region q27.1 of the X chromosome, or something specific about the inserted piece of chromosome 5.  Then DNA from the Mexican family was sequenced.  The CGH patients in that family had an insertion of chromosome 4 into region q27.1 of the X chromosome.  Clearly, the problem wasn’t caused by what was added, but rather by the disruption itself. 

Both insertions occurred within a palindromic sequence of DNA.  Although the significance of this DNA palindrome is not understood, it definitely ceased to read the same way backwards and forwards after the insertion event.  In addition, the insertions were near the SOX3 gene, which is a member of a gene family known to be involved in hair growth. 

Taken together, the researchers believe that these rare insertion events disrupted a critical palindromic sequence at the end of the X chromosome, which in turn up-regulated (turned on) the SOX3 gene.  If so, finding a way to control SOX3 could lead to a cure of both CGH and baldness.