Sequence analysis of P21-activated kinase 3 (PAK3) in chronic schizophrenia with cognitive impairment.
The P21-activated kinase PAK3 is critical for cognitive development and truncating mutations cause non-syndromic mental retardation (MR). Missense mutations are also associated with psychotic disorders, most commonly with schizophrenia involving premorbid MR, namely "pfropfschizophrenie". We set out to measure the frequency of sequence variants in PAK3 in schizophrenia without premorbid MR. We conducted complete gene reseqeuncing of all coding exons and exon-intron boundaries in patients with schizophrenia with cognitive impairment but without premorbid MR. Deleterious variants in schizophrenia alone were rare (<1/159 or 0.6%). Thereby, while PAK3 remains a strong biological candidate in psychosis, evidence from human genetics provides strongest support for a link to pfropfschizophrenie and not to schizophrenia without premorbid intellectual disability.
Morrow
Eric M
EM
Division of Neurogenetics and Howard Hughes Medical Institute, Department of Neurology, Beth Israel Deaconess Medical Center, USA.
Kane
Anna
A
Goff
Donald C
DC
Walsh
Christopher A
CA
D000293:Adolescent; D000328:Adult; D000368:Aged; D002874:Chromosome Mapping; D002908:Chronic Disease; D003072:Cognition Disorders / Q000175:diagnosis* / Q000201:enzymology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic / Q000235:genetics; D012559:Schizophrenia / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D017421:Sequence Analysis; D054462:p21-Activated Kinases / Q000235:genetics*
D054462:p21-Activated Kinases