Neuropathologic Research Strategies in Holoprosencephaly
Neuropathologic Research Strategies in Holoprosencephaly
复制标题
前脑无裂畸形的神经病理学研究策略
DOI：
--
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Laura Flores
中科院分区：
文献类型：
--
作者：
Harvey B. Samat;Laura Flores
提出了一些假说来解释无前脑畸形的几个临床特征的发病机制，并提出了检验这些假说的神经病理学方法。前脑无裂畸形的传统形态学分类为无叶型、半叶型和叶型，根据严重程度分级，每种类型都发生在所有已知的基因突变中。在人类前脑无裂畸形中被鉴定为原发性的四个缺陷基因中，三个表现出腹背侧表达梯度（SHH、SIX 3和TGIF），一个表现出背腹侧表达梯度（ZIC 2）。但是，除了垂直轴，在神经管中表达的基因在其他轴中也可能具有吻尾和中间外侧梯度。这些其他梯度可能与垂直方向同样重要。如果吻尾梯度延伸到中脑神经节，它可能会干扰中脑神经嵴的形成、迁移或凋亡，而中脑神经嵴形成面部、眼眶、鼻子和眼睛部分的膜骨，并可能解释在许多但不是所有的前脑无裂畸形儿童中看到的面中部发育不全。这种吻尾梯度也会导致尾状核、丘脑和下丘脑的不分裂，并导致前脑无裂畸形的背侧囊肿的形成，这可能是由于第三脑室的松果体上隐窝扩大，端脑单脑室继发性扩张，有时可能会产生独特的经<$颅脑膨出。内外侧梯度的程度可以解释前脑内侧部分和外侧部分正常皮质的大脑皮质结构的严重紊乱，包括放射状胶质纤维。这种保留的侧皮质可以解释为什么一些前脑无裂畸形的儿童具有比预期更好的智力功能，并且与诸如无脑畸形的畸形相比，在癫痫的发病机制中也可能是重要的，其中整个大脑皮质都参与其中。癫痫在某些情况下，但不是所有的情况下，也可能与轴突终末的顺序成熟有关的神经元，他们支配。尿崩症是大多数患者的并发症;其他神经内分泌疾病发生率较低。二次下调的OTP基因或下游基因，如BRN 2或SIM 1可能会导致失败的视上核和室旁下丘脑核的大细胞神经元的终末分化。放射状胶质纤维定向紊乱或室管膜异常可使神经上皮细胞异常迁移入脑室。前脑无裂畸形需要一个新的分类，以整合形态学和遗传学标准。（J Child Neurol 2001;16：918-931）。
Hypotheses are presented to explain the pathogenesis of several clinical features of holoprosencephaly, and neuropathologic approaches to testing these hypotheses are suggested. The traditional morphologic classification of holoprosencephaly into alobar, semilobar, and lobar forms is grades of severity, and each occurs in all of the genetic mutations known. Of the four defective genes identified as primary in human holoprosencephaly, three exhibit a ventrodorsal gradient of expression (SHH, SIX3, and TGIF) and one a dorsoventral gradient (ZIC2). But, in addition to the vertical axis, genes expressed in the neural tube also may have rostrocaudal and mediolateral gradients in the other axes. These other gradients may be equally as important as the vertical. If the rostrocaudal gradient extends as far as the mesencephalic neuromere, it may interfere with the formation, migration, or apoptosis of the mesencephalic neural crest, which forms membranous bones of the face, orbits, nose, and parts of the eyes, and may explain the midfacial hypoplasia seen in many, but not all, children with holoprosencephaly. This rostrocaudal gradient also causes noncleavage of the caudate nucleus, thalamus, and hypothalamus and contributes to the formation of the dorsal cyst of holoprosencephaly, which is probably derived from an expanded suprapineal recess of the 3rd ventricle with secondary dilation of the telencephalic monoventricle and at times may produce a unique transfontanellar encephalocele. The extent of the mediolateral gradient may explain the severe disorganization of cerebral cortical architecture in medial parts of the forebrain and normal cortex in lateral parts, including the radial glial fibers. This preserved lateral cortex may explain why some children with holoprosencephaly have better intellectual function than expected and may also be important in the pathogenesis of epilepsy, by contrast with malformations such as lissencephaly, in which the entire cerebral cortex is involved. Epilepsy in some, but not all, cases also may be related to the sequential maturation of axonal terminals in relation to the neurons they innervate. Diabetes insipidus is a complication in a majority of patients; other neuroendocrinopathies occur less frequently. Secondary down-regulation of the OTP gene or of downstream genes such as BRN2 or SIM1 may result in failure of terminal differentiation of magnocellular neurons of the supraoptic and paraventricular hypothalamic nuclei. Disoriented radial glial fibers or abnormal ependyma may allow aberrant migration of neuroepithelial cells into the ventricle. A new classification of holoprosencephaly is needed to integrate morphologic and genetic criteria. (J Child Neurol 2001;16:918-931).
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影响因子：
3.5
作者：
Brown, LY;Odent, S;Muenke, M
通讯作者：
Muenke, M
含有人类同源结构域的基因 Orthopedia (OTP) 的鉴定、染色体分配和表达分析。
影响因子：
4.4
作者：
Lin,X;State,MW;Vaccarino,FM;Greally,J;Hass,M;Leckman,JF
通讯作者：
Leckman,JF
影响因子：
4.6
作者：
Hua Shun Li;Christopher Tierney;L. Wen;Jane Y. Wu;Yi Rao
通讯作者：
Hua Shun Li;Christopher Tierney;L. Wen;Jane Y. Wu;Yi Rao
前脑无裂畸形深部灰色核的评估。
DOI：
--
发表时间：
2000
期刊：
AJNR. American journal of neuroradiology
影响因子：
--
作者：
Simon,EM;Hevner,R;Pinter,JD;Clegg,NJ;Miller,VS;Kinsman,SL;Hahn,JS;Barkovich,AJ
通讯作者：
Barkovich,AJ