CNTNAP2 is disrupted in a family with Gilles de la Tourette syndrome and obsessive compulsive disorder.
Gilles de la Tourette syndrome (GTS) is a sporadic or inherited complex neuropsychiatric disorder characterized by involuntary motor and vocal tics. There is comorbidity with disorders like obsessive compulsive disorder and attention deficit hyperactivity disorder. Until now linkage analysis has pointed to a number of chromosomal locations, but has failed to identify a clear candidate gene(s). We have investigated a GTS family with a complex chromosomal insertion/translocation involving chromosomes 2 and 7. The affected father [46,XY,inv(2) (p23q22),ins(7;2) (q35-q36;p21p23)] and two affected children [46,XX,der(7)ins(7;2)(q35-q36;p21p23) and 46,XY,der(7)ins(7;2)(q35-q36;p213p23)] share a chromosome 2p21-p23 insertion on chromosome 7q35-q36, thereby interrupting the contactin-associated protein 2 gene (CNTNAP2). This gene encodes a membrane protein located in a specific compartment at the nodes of Ranvier of axons. We hypothesize that disruption or decreased expression of CNTNAP2 could lead to a disturbed distribution of the K(+) channels in the nervous system, thereby influencing conduction and/or repolarization of action potentials, causing unwanted actions or movements in GTS.
Verkerk
Annemieke J M H
AJ
Department of Clinical Genetics, Erasmus MC, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands.
Mathews
Carol A
CA
Joosse
Marijke
M
Eussen
Bert H J
BH
Heutink
Peter
P
Oostra
Ben A
BA
D002675:Child, Preschool; D002889:Chromosomes, Human, Pair 2; D002897:Chromosomes, Human, Pair 7; D015897:Comorbidity; D005260:Female; D006801:Humans; D007621:Karyotyping; D008297:Male; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009771:Obsessive-Compulsive Disorder / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D010375:Pedigree; D005879:Tourette Syndrome / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D014178:Translocation, Genetic
C403049:CNTNAP2 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins