title: Altered structural brain connectome in young adult fragile X premutation carriers.
abstract: Fragile X premutation carriers (fXPC) are characterized by 55-200 CGG trinucleotide repeats in the 5' untranslated region on the Xq27.3 site of the X chromosome. Clinically, they are associated with the fragile X-Associated Tremor/Ataxia Syndrome, a late-onset neurodegenerative disorder with diffuse white matter neuropathology. Here, we conducted first-ever graph theoretical network analyses in fXPCs using 30-direction diffusion-weighted magnetic resonance images acquired from 42 healthy controls aged 18-44 years (HC; 22 male and 20 female) and 46 fXPCs (16 male and 30 female). Globally, we found no differences between the fXPCs and HCs within each gender for all global graph theoretical measures. In male fXPCs, global efficiency was significantly negatively associated with the number of CGG repeats. For nodal measures, significant group differences were found between male fXPCs and male HCs in the right fusiform and the right ventral diencephalon (for nodal efficiency), and in the left hippocampus [for nodal clustering coefficient (CC)]. In female fXPCs, CC in the left superior parietal cortex correlated with counting performance in an enumeration task.
authors.affiliation: Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois; Department of Bioengineering, University of Illinois at Chicago, Chicago, Illinois, and Community Psychiatry, Sacramento, California.
authors.forename: Alex
authors.initials: A
authors.lastname: Leow
authors.forename: Danielle
authors.initials: D
authors.lastname: Harvey
authors.forename: Naomi J
authors.initials: NJ
authors.lastname: Goodrich-Hunsaker
authors.forename: Johnson
authors.initials: J
authors.lastname: Gadelkarim
authors.forename: Anand
authors.initials: A
authors.lastname: Kumar
authors.forename: Liang
authors.initials: L
authors.lastname: Zhan
authors.forename: Susan M
authors.initials: SM
authors.lastname: Rivera
authors.forename: Tony J
authors.initials: TJ
authors.lastname: Simon
mesh_terms: D000293:Adolescent; D000328:Adult; D001259:Ataxia / Q000235:genetics; D001921:Brain / Q000473:pathology*; D041321:Chromosomes, Human, X / Q000235:genetics*; D063132:Connectome; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000235:genetics; D006801:Humans; D008297:Male; D008959:Models, Neurological; D009434:Neural Pathways / Q000473:pathology; D009929:Organ Size; D011581:Psychological Tests; D012727:Sex Characteristics; D014202:Tremor / Q000235:genetics; D019680:Trinucleotide Repeat Expansion; D055815:Young Adult
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human
keywords: CGG; DTI; FXTAS; fragile X; graph theory; structural connectome