PT  - JOURNAL ARTICLE
AU  - Joe Bathelt
AU  - Jessica Barnes
AU  - F Lucy Raymond
AU  - Kate Baker
AU  - Duncan Astle
TI  - Global and local connectivity differences converge with gene expression in a neurodevelopmental disorder of known genetic origin
AID  - 10.1101/057687
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 057687
4099  - http://biorxiv.org/content/early/2016/06/07/057687.short
4100  - http://biorxiv.org/content/early/2016/06/07/057687.full
AB  - Knowledge of genetic cause in neurodevelopmental disorders can highlight molecular and cellular processes critical for typical development. Furthermore, the relative homogeneity of neurodevelopmental disorders of known genetic origin allows the researcher to establish the subsequent neurobiological processes that mediate cognitive and behavioural outcomes. The current study investigated white matter structural connectivity in a group of individuals with intellectual disability due to mutations in ZDHHC9. In addition to shared cause of cognitive impairment, these individuals have a shared cognitive profile, involving oro-motor control difficulties and expressive language impairment. Analysis of structural network properties using graph theory measures showed global reductions in mean clustering coefficient and efficiency in the ZDHHC9 group, with maximal differences in frontal and parietal areas. Regional variation in clustering coefficient and local efficiency across cortical regions in cases and controls were significantly associated with known pattern of expression of ZDHHC9 in the normal adult human brain. The results demonstrate that a mutation in a single gene impacts upon white matter organisation across the whole-brain, but also shows regionally specific effects, according to variation in gene expression. Furthermore, these regionally specific patterns may link to specific developmental mechanisms, and correspond to specific cognitive deficits.