Highly Qualified Public School Teacher: Its Status

Tourette syndrome (TS) is an inherited neuropsychiatric disorder that is characterized by chronic motor and vocal tics.

The clinical heterogeneity of the disorder is truly a complicating factor in elucidating the genetic basis for the disorder.

It may be that there is no definitive causative gene for TS, but multiple contributing alleles.

By identifying rare TS cases and associated rare variants, we can gain insight into the gene pathway(s) involved in the pathophysiology of TS.

We used this rare variant approach to identify a promising gene, Slit and Trk-like family member 1 (SLITRK1), in a TS patient with a chromosomal abnormality.

The function of SLITRK1 is not known and therefore we sought to further characterize SLITRK1 through expression analyses and identification of binding partners.

We found that SLITRK1 is developmentally regulated in the cortico-striatal circuitry, which is implicated in TS.

Despite multiple screens for interactors for the extracellular domain of SLITRK1, none were identified.

However, expression profiling of SLITRK1 cell lines has lead to several potential and interesting pathways.

Recently, through genetic analysis of a rare TS pedigree, we also identified a causative mutation in the gene Histidine Decarboxylase (HDC).

Functional analysis determined that this mutation resulted in a dominant negative phenotype.

The histaminergic pathway is a strong candidate for a causal mechanism in TS.

Through identification and characterization of these rare variants associated with TS, we hope to further our understanding of the mechanisms contributing to the pathophysiology of TS.