Those following the story will know that chasing the genes that cause Tourette syndrome can seem like the quest for the end of an apparently very visible rainbow.

This week there is more of the same with three new findings, one of which has been published by the Yale group in one of the most prestigious medical journals, the New England Journal of Medicine.

The original technique for gene-chasing from the 1980s onwards is to find families with multiple people affected by TS, then try and find genes that are different in the affected versus the non-affected members of the family (see previous blog posts below). This hasn't got us very far to date, but a gene has been found in one particular family with an affected father of eight affected children- you can see the family tree in the paper.

Genetic techniques have advanced out of all recognition in the last 25 years, so that now examing the DNA of each family member is far quicker and more detailed than could have been dreamt of in the past. The importance of this study is that, in this particular family, an abnormal gene present in those with TS was identified. This was a mutation of the gene for an enyzme called HDC that makes the chemical histamine. This name may be familiar for anyone taking anti-histamine pills- histamine is associated with allergy mechanisms but is also present in the brain and can act as a neurotransmitter. Previous work in mice has shown that abnormalities of this gene can cause repetitive behaviours which could be compared to tics. The importance of this is that it could indicate that we should look at the histamine system as a possible way of treating TS.

Does anyone find that taking piriton or phenergan makes their tics better or worse? (The more modern antistamines cause less sedation because they have less effect on the brain so we wouldn't expect them to have much effect on tics).

As is so often the case this is a preliminary finding- what is now needed is a search for the HDC mutation in other people with TS who are not members of this one family.

Moving on to the second study, from Columbia, that is not particularly novel, but once more implicates and confirms the involvement of the dopamine system. Neurotransmitters are released from nerve cells (neurons) at a gap called a synapse and then pass on the nerve impulse to the next nerve cell by attaching to a specific "receptor". In this study of 69 TS patients the gene for one of the dopamine receptors (called DRD2) was examined and it was found that people with TS were more likely to have particular variants thereby suggesting that dopamine dysfunction is important in TS.

The third study is more novel, using newer concepts. When James Watson and the late Francis Crick made their famous Nobel Prize winning discovery of the genetic code in the 1960s and the gene for Huntington's disease was subsequently identified in the 1980s it looked like we had cracked the code to every genetic disease, given enough time. In recent years it has become apparent that there is a lot about our DNA that is not yet fully understood.

Whilst the genetic code tell us what proteins are made in cells, our chromosomes also contain vast tracts of DNA that are “non-coding”- i.e. are not used to produce proteins but may be involved in the regulation of cellular function in other ways that are not yet well understood. Another aspect of our DNA that could be significant is that certain sections of it are deleted or duplicated in different individuals- this is called copy number variants (CNV).

Thousands of these variants have been identified. In this study of 111 TS patients, 10 of them were found to have one of five rare CNVs that were not found in controls. The basic logic is similar to the second paper- trying to find genetic variations that mark out people with TS, without having to find large familes with multiple affected members. Three of these five CNVs have also previously been found in autism, schizophrenia and ADHD. The suggestion is that some CNVs may be present in a spectrum of neuropsychiatric problems, not just TS.

As the study was relatively small and can be technically criticised in some other ways, this again can only be considered a preliminary pointer and not a ready-made breakthrough. There will be much more of this kind of work in future- including from the American TSAs International Genetic Consortium.