Department of Developmental Neurobiology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314, USA.
J Neuropathol Exp Neurol. 2012 May;71(5):382-97. doi: 10.1097/NEN.0b013e318251f537.
The purposes of this study were to identify differences in patterns of developmental abnormalities between the brains of individuals with autism of unknown etiology and those of individuals with duplications of chromosome 15q11.2-q13 (dup[15]) and autism and to identify alterations that may contribute to seizures and sudden death in the latter. Brains of 9 subjects with dup(15), 10 with idiopathic autism, and 7 controls were examined. In the dup(15) cohort, 7 subjects (78%) had autism, 7 (78%) had seizures, and 6 (67%) had experienced sudden unexplained death. Subjects with dup(15) autism were microcephalic, with mean brain weights 300 g less (1,177 g) than those of subjects with idiopathic autism (1,477 g; p<0.001). Heterotopias in the alveus, CA4, and dentate gyrus and dysplasia in the dentate gyrus were detected in 89% of dup(15) autism cases but in only 10% of idiopathic autism cases (p < 0.001). By contrast, cerebral cortex dysplasia was detected in 50% of subjects with idiopathic autism and in no dup(15) autism cases (p<0.04). The different spectrum and higher prevalence of developmental neuropathologic findings in the dup(15) cohort than in cases with idiopathic autism may contribute to the high risk of early onset of seizures and sudden death.
本研究旨在鉴定病因不明的自闭症个体与 15q11.2-q13 染色体重复（dup[15]）伴自闭症个体的脑发育异常模式的差异，并鉴定可能导致后者癫痫发作和猝死的改变。对 9 例 dup(15)、10 例特发性自闭症和 7 例对照者的脑进行了检查。在 dup(15)组中，7 例（78%）有自闭症，7 例（78%）有癫痫发作，6 例（67%）经历了无法解释的突发性死亡。dup(15)自闭症患者存在小头畸形，脑重平均减少 300 克（1177 克），低于特发性自闭症患者（1477 克；p<0.001）。89%的 dup(15)自闭症病例中检测到肺泡、CA4 和齿状回的异位和齿状回的发育不良，但在 10%的特发性自闭症病例中检测到（p<0.001）。相比之下，50%的特发性自闭症患者存在皮质发育不良，而在 dup(15)自闭症患者中未检测到（p<0.04）。dup(15)组比特发性自闭症患者具有更广泛和更高发生率的发育性神经病理学发现，这可能导致癫痫发作和猝死的早期发生风险增加。
