Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA.
J Med Genet. 2011 Feb;48(2):141-4. doi: 10.1136/jmg.2010.082263. Epub 2010 Oct 23.
Cerebral palsy is a heterogeneous group of neurodevelopmental brain disorders resulting in motor and posture impairments often associated with cognitive, sensorial, and behavioural disturbances. Hypoxic-ischaemic injury, long considered the most frequent causative factor, accounts for fewer than 10% of cases, whereas a growing body of evidence suggests that diverse genetic abnormalities likely play a major role.
This report describes an autosomal recessive form of spastic tetraplegic cerebral palsy with profound intellectual disability, microcephaly, epilepsy and white matter loss in a consanguineous family resulting from a homozygous deletion involving AP4E1, one of the four subunits of the adaptor protein complex-4 (AP-4), identified by chromosomal microarray analysis.
These findings, along with previous reports of human and mouse mutations in other members of the complex, indicate that disruption of any one of the four subunits of AP-4 causes dysfunction of the entire complex, leading to a distinct 'AP-4 deficiency syndrome'.
脑瘫是一组异质性的神经发育性脑障碍，导致运动和姿势障碍，常伴有认知、感觉和行为障碍。缺氧缺血性损伤长期以来被认为是最常见的致病因素，但越来越多的证据表明，多种遗传异常可能起主要作用。
本报告描述了一个常染色体隐性遗传形式的痉挛性四肢瘫痪性脑瘫，伴有严重的智力残疾、小头畸形、癫痫和白质丢失，在一个由同源性缺失引起的近亲家庭中，该缺失涉及 AP4E1，即衔接蛋白复合物-4 (AP-4) 的四个亚单位之一，通过染色体微阵列分析确定。
这些发现以及以前在其他成员的人类和小鼠突变报告表明，AP-4 的四个亚单位中的任何一个的破坏都会导致整个复合物的功能障碍，导致一个独特的“AP-4 缺乏综合征”。
