Seattle Children's Research Institute, 1900 Ninth Ave,, Box C9S-10, Seattle, WA 98101, USA.
Acta Neuropathol Commun. 2013 Aug 2;1:45. doi: 10.1186/2051-5960-1-45.
Monosomy 1p36 is the most common subtelomeric chromosomal deletion linked to mental retardation and seizures. Neuroimaging studies suggest that monosomy 1p36 is associated with brain malformations including polymicrogyria and nodular heterotopia, but the histopathology of these lesions is unknown. Here we present postmortem neuropathological findings from a 10 year-old girl with monosomy 1p36, who died of respiratory complications. The findings included micrencephaly, periventricular nodular heterotopia in occipitotemporal lobes, cortical dysgenesis resembling polymicrogyria in dorsolateral frontal lobes, hippocampal malrotation, callosal hypoplasia, superiorly rotated cerebellum with small vermis, and lumbosacral hydromyelia. The abnormal cortex exhibited "festooned" (undulating) supragranular layers, but no significant fusion of the molecular layer. Deletion mapping demonstrated single copy loss of a contiguous 1p36 terminal region encompassing many important neurodevelopmental genes, among them four HES genes implicated in regulating neural stem cell differentiation, and TP73, a monoallelically expressed gene. Our results suggest that brain and spinal malformations in monosomy 1p36 may be more extensive than previously recognized, and may depend on the parental origin of deleted genes. More broadly, our results suggest that specific genetic disorders may cause distinct forms of cortical dysgenesis.
单体性 1p36 是与智力障碍和癫痫相关的最常见的亚端粒染色体缺失。神经影像学研究表明，单体性 1p36 与脑畸形有关，包括多微小脑回和结节性异位，但这些病变的组织病理学尚不清楚。在这里，我们介绍了一名 10 岁女孩单体性 1p36 的死后神经病理学发现，该女孩因呼吸并发症死亡。发现包括小头畸形、枕颞叶的脑室周围结节性异位、背外侧额叶类似于多微小脑回的皮质发育不良、海马旋转不良、胼胝体发育不良、上旋小脑伴小蚓部、腰骶部脊髓空洞症。异常皮质显示出“皱襞状”（波浪状）的颗粒层，但分子层没有明显融合。缺失图谱显示，一个连续的 1p36 末端区域的单拷贝丢失，该区域包含许多重要的神经发育基因，其中包括四个与调节神经干细胞分化有关的 HES 基因，以及单等位基因表达的基因 TP73。我们的结果表明，单体性 1p36 的脑和脊髓畸形可能比以前认识到的更为广泛，并且可能取决于缺失基因的亲本来源。更广泛地说，我们的结果表明，特定的遗传疾病可能导致不同形式的皮质发育不良。
