title: Evidence for association between structural variants in lissencephaly-related genes and executive deficits in schizophrenia or bipolar patients from a Spanish isolate population.
abstract: There is evidence for an association between structural variants in genes for lissencephaly, which are involved in neuronal migration, and prefrontal cognitive deficits in schizophrenia and bipolar patients. On the basis of these intriguing findings, we analyzed 16 markers located in the lissencephaly critical region (LCR in chromosome 17p13.3) in 124 schizophrenic, 56 bipolar, and 141 healthy individuals. All recruits were from a Spanish population isolate of Basque origin that is characterized by low genetic heterogeneity. In addition, we examined whether structural genomic variations in the LCR were associated with executive cognition. Twenty-three patients (12.8%), but none of the controls, showed structural variants (deletions and insertions) in either of two markers related with lissencephaly (D17S1566 on tumor suppressor gene TP53: tumor protein p53 and D17S22 on SMG6 gene: Smg-6 homolog, nonsense mediated mRNA decay factor- Caenorhabditis elegans). These patients performed significantly worse in the Wisconsin Card Sorting Test-Categories in comparison with patients without such variations in lissencephaly-related genes. The presence of structural variants was related to completed categories, and accounted for 10.7% of the variance (P=0.001). Finally, logistic regression showed that poor Wisconsin Card Sorting Test-Categories performance was the only predictor of belonging to the positive LCR variations group. These new findings provide further evidence for the association between some lissencephaly-related genes and both schizophrenia and bipolar disorder, and influence on frontal executive functioning.
authors.affiliation: Department of Medicine, University of Valencia, Valencia, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Tabarés-Seisdedos
authors.forename: Ignacio
authors.initials: I
authors.lastname: Mata
authors.forename: Teresa
authors.initials: T
authors.lastname: Escámez
authors.forename: Eduard
authors.initials: E
authors.lastname: Vieta
authors.forename: Jose M
authors.initials: JM
authors.lastname: López-Ilundain
authors.forename: Jose
authors.initials: J
authors.lastname: Salazar
authors.forename: Gabriel
authors.initials: G
authors.lastname: Selva
authors.forename: Vicente
authors.initials: V
authors.lastname: Balanzá
authors.forename: Cristina
authors.initials: C
authors.lastname: Rubio
authors.forename: Anabel
authors.initials: A
authors.lastname: Martínez-Arán
authors.forename: Lourdes
authors.initials: L
authors.lastname: Valdés-Sánchez
authors.forename: Emilio
authors.initials: E
authors.lastname: Geijo-Barrientos
authors.forename: Salvador
authors.initials: S
authors.lastname: Martínez
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics* / Q000523:psychology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D054082:Lissencephaly / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012559:Schizophrenia / Q000235:genetics*; D013030:Spain