White matter abnormalities in 22q11.2 deletion syndrome: preliminary associations with the Nogo-66 receptor gene and symptoms of psychosis.

[22q11.2 deletion syndrome]

This study utilized diffusion tensor imaging (DTI ) to analyze white matter tractography in the anterior limb of the internal capsule (ALIC ), fornix , and uncinate fasciculus (UF ) of individuals with 22 q 11 .2 deletion syndrome and controls . Aberrations in these tracts have been previously associated with schizophrenia . With up to 25 % of individuals with 22 q 11 .2 DS developing schizophrenia in adulthood , we hypothesized reduction in structural integrity of these tracts , including an association with prodromal symptoms of psychosis . We further predicted an association between allelic variation in a functional polymorphism of the Nogo-66 receptor gene and 22 q 11 .2 DS white matter integrity .Tractography was conducted using fiber assignment by streamline tracking algorithm in DTI Studio . Subjects were genotyped for the rs 701428 SNP of the Nogo-66 receptor gene , and assessed for presence of prodromal symptoms .We found significant group differences between 22 q 11 .2 DS and controls in DTI metrics for all three tracts . DTI metrics of ALIC and UF were associated with prodromal symptoms in 22 q 11 .2 DS . Further , ALIC DTI metrics were associated with allelic variation of the rs 701428 SNP of the Nogo-66 receptor gene in 22 q 11 .2 DS .Alterations in DTI metrics suggest white matter microstructural anomalies of the ALIC , fornix , and UF in 22 q 11 .2 DS . Structural differences in ALIC appear to be associated with the Nogo-66 receptor gene , which has been linked to myelin-mediated axonal growth inhibition . Moreover , the association between psychosis symptoms and ALIC and UF metrics suggests that the Nogo-66 receptor gene may represent a susceptibility gene for psychosis through its disruption of white matter microstructure and myelin-associated axonal growth .

Diseases
Validation

Diseases presenting "schizophrenia" symptom

22q11.2 deletion syndrome

achondroplasia

alexander disease

cadasil

child syndrome

congenital toxoplasmosis

kabuki syndrome

kallmann syndrome

krabbe disease

neuralgic amyotrophy

oligodontia

oral submucous fibrosis

zellweger syndrome

This symptom has already been validated