Disease relevance of CNTNAP2

• We analysed by immunohistochemistry on free-floating sections from multiple sclerosis brains the expression and distribution of nodal (Na(v) channels), paranodal (paranodin/Caspr) and juxtaparanodal (K(v) channels and Caspr2) molecules in demyelinated and remyelinated lesions [1].

Psychiatry related information on CNTNAP2

• CNTNAP2 is disrupted in a family with Gilles de la Tourette syndrome and obsessive compulsive disorder [2].

High impact information on CNTNAP2

• This association involves the C-terminal sequence of Caspr2, which contains a putative PDZ binding site [3].
• 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 [2].
• 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) [2].
• Although ultrastructural studies indicate that paranodal complexes are linked to the cytoskeleton, the intracellular partners of Caspr/paranodin, as well as those of Caspr2, are poorly characterized [4].
• To study the human contactin-associated protein-like 2 gene (CNTNAP2), we have determined its complete DNA sequence and its genomic organization to comprise 25 exons spanning greater than 2.0 Mb of DNA at 7q35 [5].

Anatomical context of CNTNAP2

• Temporal-lobe specimens showed evidence of abnormalities of neuronal migration and structure, widespread astrogliosis, and reduced expression of CASPR2 [6].
• Contactin-associated protein-like 2 (CASPR2) is encoded by CNTNAP2 and clusters voltage-gated potassium channels (K(v)1.1) at the nodes of Ranvier [6].

Other interactions of CNTNAP2

• We report a homozygous mutation of CNTNAP2 in Old Order Amish children with cortical dysplasia, focal epilepsy, relative macrocephaly, and diminished deep-tendon reflexes [6].
• In contrast to the demyelinated plaques, all remyelinated lesions are characterized by the detection of aggregates of Na(v) channels, paranodin/Caspr, K(v) channels and Caspr2 [1].

References