Autosomal recessive primary microcephaly (MCPH) is a uncommon disorder due to congenital deficiency in the development of the cerebral cortex, characterized by a head circumference below 2 SD. MCPH is a group of diseases with genetic heterogeneity and has been reported by the Online Mendelian Inheritance In Man® (OMIM) database and associated with 25 different genes. It is known that MCPH cases are most frequently associated with abnormal spindle-like, microcephaly-associated (ASPM) gene mutations. The ASPM protein consists of an N-terminal 81 IQ (isoleucine-glutamine) domain, a calponin-homology domain, and a C-terminal domain. It interacts with calmodulin and calmodulin-related proteins via the IQ domain and acts as a part in mitotic spindle function. The basic characteristics of cases with ASPM gene mutations are microcephaly (below −3 SD) present before 1 year of age, intellectual disability, and the absence of other congenital anomalies. Macroscopic organization of the brain is preserved in cases with ASPM mutation, and a decrease in brain volume, particularly gray matter volume loss and a simplified gyral pattern are observed. Cortical migration defects are a very rare finding in patients with ASPM mutations. In the present study, we aimed to discuss the clinical and genetic findings in 2 cases with cortical dysplasia in which truncated variants in the ASPM gene were detected, particularly in terms of genotype-phenotype correlation in comparison with the literature.
Mol Syndromol

中文翻译：

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ASPM基因截短突变导致原发性小头畸形2例新发神经元迁移缺陷

常染色体隐性遗传原发性小头畸形 (MCPH) 是一种罕见的疾病，由于大脑皮层发育的先天性缺陷，其特征是头围低于 2 SD。MCPH 是一组具有遗传异质性的疾病，已被在线孟德尔遗传® (OMIM) 数据库报告，并与 25 个不同的基因相关。众所周知，MCPH 病例最常与异常的纺锤样、小头畸形相关 ( ASPM ) 基因突变相关。ASPM 蛋白由一个 N 端 81 IQ（异亮氨酸-谷氨酰胺）结构域、一个钙调蛋白同源结构域和一个 C 端结构域组成。它通过 IQ 域与钙调蛋白和钙调蛋白相关蛋白相互作用，并作为有丝分裂纺锤体功能的一部分。ASPM病例的基本特征基因突变是1 岁前出现的小头畸形（低于- 3 SD）、智力障碍和没有其他先天性异常。在ASPM突变的情况下，大脑的宏观组织得以保留，并且观察到脑容量减少，特别是灰质体积减少和简化的脑回模式。皮质迁移缺陷在ASPM突变患者中非常罕见。在本研究中，我们旨在讨论 2 例皮层发育不良患者的临床和遗传学发现，其中检测到了ASPM基因的截短变异，特别是与文献相比，在基因型-表型相关性方面。
摩尔综合症