1. ¹Department of Bioinformatics, Erasmus Medical Center, Rotterdam, The Netherlands
2. ²Department of Psychiatry, VU Medical Center/Academic Anxiety Outpatient Clinic, GGZ Buitenamstel, Amsterdam, The Netherlands
3. ³Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands
4. ⁴Section of Medical Genomics, Department of Human Genetics, VU University Medical Center, and Center for Neurogenomics and Cognitive Research, VU University and VU University Medical Center, Amsterdam, The Netherlands
5. ⁵Department of Epidemiology & Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands

Correspondence: Dr AJMH Verkerk, Department of Bioinformatics, Erasmus Medical Center, PO Box 1738, 3000DR Rotterdam, The Netherlands. E-mail: j.verkerk@erasmusmc.nl

⁶These authors contributed equally to this paper.

Received 4 April 2006; Revised 13 June 2006; Accepted 27 June 2006; Published online 8 August 2006.

Abstract

Gilles de la Tourette syndrome is a complex neuropsychiatric disorder, which becomes evident in childhood between the ages of 2 and 15 years. Tourette syndrome is defined by the occurrence of a large range and variable number of unwanted repetitive simple or complex motor and vocal tics that start in childhood and follow a waxing and waning course. A major gene for this syndrome has not yet been identified, probably owing to both genetic and phenotypic heterogeneity of this disease. This article describes the clinical evaluation of patients and family members in a large Dutch Gilles de la Tourette Syndrome pedigree and the decisions encountered with respect to phenotyping. The importance of an accurate definition of the Tourette phenotype is discussed, which is highly important for reliable genetic linkage and association studies. Subsequent linkage analysis resulted in three linkage peaks on different chromosomes 3q, 9q, and 13q. Multipoint analysis resulted in a single linkage peak with logarithm of odds score 2.55 with marker D3S1311 on chromosome 3q.