The Effects of X Chromosome Loss on Neuroanatomical and Cognitive Phenotypes During Adolescence: a Multi-modal Structural MRI and Diffusion Tensor Imaging Study.
The absence of all or part of one X chromosome in female humans causes Turner's syndrome (TS), providing a unique "knockout model" to investigate the role of the X chromosome in neuroanatomy and cognition. Previous studies have demonstrated TS-associated brain differences; however, it remains largely unknown 1) how the brain structures are affected by the type of X chromosome loss and 2) how X chromosome loss influences the brain-cognition relationship. Here, we addressed these by investigating gray matter morphology and white matter connectivity using a multimodal MRI dataset from 34 adolescent TS patients (13 mosaic and 21 nonmosaic) and 21 controls. Intriguingly, the 2 TS groups exhibited significant differences in surface area in the right angular gyrus and in white matter integrity of the left tapetum of corpus callosum; these data support a link between these brain phenotypes and the type of X chromosome loss in TS. We further showed that the X chromosome modulates specific brain-cognition relationships: thickness and surface area in multiple cortical regions are positively correlated with working-memory performance in controls but negatively in TS. These findings provide novel insights into the X chromosome effect on neuroanatomical and cognitive phenotypes and highlight the role of genetic factors in brain-cognition relationships.
Department of Radiology, China-Japan Friendship Hospital, Beijing 100029, China.
Sheng
S
Xie
Department of Pediatrics, China-Japan Friendship Hospital, Beijing 100029, China.
Zhixin
Z
Zhang
Department of Pediatrics, China-Japan Friendship Hospital, Beijing 100029, China.
Qiuling
Q
Zhao
State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University, Beijing 100875, China.
Jiaying
J
Zhang
State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University, Beijing 100875, China.
Suyu
S
Zhong
State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University, Beijing 100875, China.
Yanchao
Y
Bi
State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University, Beijing 100875, China.
Yong
Y
He
Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.
Hui
H
Pan
State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University, Beijing 100875, China.
Gaolang
G
Gong
D000293:Adolescent; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping; D016022:Case-Control Studies; D002648:Child; D041321:Chromosomes, Human, X / Q000235:genetics*; D003072:Cognition Disorders / Q000209:etiology*; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D009483:Neuropsychological Tests; D010641:Phenotype; D014424:Turner Syndrome / Q000150:complications / Q000235:genetics / Q000473:pathology
Turner's syndrome; diffusion tensor imaging (DTI); gray matter morphology; magnetic resonance imaging (MRI); the X chromosome; white matter connectivity