文摘
摘要目的:描述一个表型ATP1A3突变引起的频谱。
背景:最近ATP1A3突变已被证明导致越来越多的疾病不同的表型包括急性肌张力障碍震颤麻痹(RDP),交替半身不遂的童年(AHC),复发性脑病/小脑性共济失调和枕综合症。在这里,我们描述一个新的实体,表现为肌张力障碍、先天性畸形(眼睛、鼻子、上唇和其他),脑病包括发育迟缓、MRI异常(小脑萎缩,有时其他的发现),没有偏瘫(Ø)(D-DEMØ)。
设计/方法:回顾在我们的AHC ATP1A3突变的情况下,相关疾病数据库不符合任何之前的表型。
结果:所有4例共享每个和所有上述特点和震动(可能是小脑的起源)。都有全外显子组测序显示以前未报告的疾病导致ATP1A3突变。例1 (c。1079C>G, p.Thr360Arg), 3-year-old, presented neonatally with tremors, autonomic dysfunction, oculomotor abnormalities, persistent quadriplegia and dystonia, complex partial seizures, with cerebellar atrophy and bilateral cortical dysplasia on MRI. She later developed infantile spasms. Case 2 (c.420G>T, p.Gln140His), 18-year-old had onset of complex partial seizures at age 2 months, followed by autonomic dysfunction starting at age 5 months, and dystonia starting in early adolescence. Case 3 (c.974G>A, Gly325Asp), 13-year-old, presented with persistent dystonia and hypotonia starting in infancy, followed by spasticity and ataxia since early childhood. In addition to cerebellar atrophy, MRI showed pontine hypoplasia. Case 4 (c.971A>G, p.Glu324Gly), 10-year-old, presented with neonatal seizures, nystagmus and later in childhood, dystonia. None of the mutations were previously reported, and all were in or near the portion coding for transmembrane sites of the protein, similar to AHC-causing mutations. This suggests a possible link between the pump’s molecular configuration and the expressed phenotype.
结论:这四例描述小说独特的表型ATP1A3突变造成的。
研究支持:我们要感谢CureAHC基金会的慷慨资助和后勤支持。
披露:Prange博士没有披露。沙市博士没有披露。赫尔曼博士没有披露。Schiffmann博士没有披露。度琪明博士没有披露。Jasien博士没有披露。Kansagra博士没有披露。麦克莱恩博士没有披露。韦利博士没有披露。阿扎尔的博士没有披露。 Dr. Heinzen has nothing to disclose. Dr. Mikati has nothing to disclose.
