Gothelf Doron, Searcy Yvonne M, Reilly Judy, Lai Philip T, Lanre-Amos Tope, Mills Debra, Korenberg Julie R, Galaburda Albert, Bellugi Ursula, Reiss Allan L
Behavioral Neurogenetics Center, Department of Child Psychiatry, Schneider Children's Medical Center of Israel, Petah Tiqwa, Israel.
Am J Med Genet A. 2008 Nov 1;146A(21):2753-61. doi: 10.1002/ajmg.a.32507.
Williams syndrome (WS) is a neurogenetic disorder resulting from a hemizygous microdeletion at band 7q11.23. It is characterized by aberrant development of the brain and a unique profile of cognitive and behavioral features. We sought to identify the neuroanatomical abnormalities that are most strongly associated with WS employing signal detection methodology. Once identified with a Quality Receiver Operating Characteristic Curve (QROC), we hypothesized those brain regions distinguishing subjects with WS from controls would be linked to the social phenotype of individuals with this disorder. Thirty-nine adolescents and young adults with WS and 40 typically developing controls matched for age and gender were studied. The QROC identified a combination of an enlarged ventral anterior prefrontal cortex and large bending angle of the corpus callosum to distinguish between WS and controls with a sensitivity of 85.4% and specificity of 75.0%. Within the WS group, bending angle significantly correlated with ventral anterior prefrontal cortex size but not with other morphometric brain measures. Ventral anterior prefrontal size in subjects with WS was positively associated with the use of social engagement devices in a narrative task assessing the use of social and affective language. Our findings suggest that aberrant morphology of the ventral anterior prefrontal cortex is a pivotal contributing factor to the abnormal size and shape of the cerebral cortex and to the social-affective language use typical of individuals with WS.
威廉姆斯综合征（WS）是一种神经遗传疾病，由7号染色体长臂11.23带的半合子微缺失引起。其特征是大脑发育异常以及独特的认知和行为特征。我们试图采用信号检测方法来确定与WS最密切相关的神经解剖学异常。一旦通过质量接收者操作特征曲线（QROC）确定，我们假设那些区分WS患者与对照组的脑区将与该疾病个体的社会表型相关。对39名患有WS的青少年和青年以及40名年龄和性别匹配的正常发育对照进行了研究。QROC确定腹侧前额叶皮质增大和胼胝体大弯曲角度的组合可区分WS患者与对照组，敏感性为85.4%，特异性为75.0%。在WS组中，弯曲角度与腹侧前额叶皮质大小显著相关，但与其他脑形态测量指标无关。在一项评估社交和情感语言使用的叙事任务中，WS患者的腹侧前额叶大小与社交参与工具的使用呈正相关。我们的研究结果表明，腹侧前额叶皮质的异常形态是导致大脑皮质异常大小和形状以及WS患者典型社交情感语言使用的关键因素。
