PDF(Pubmed)
Abstract：
Biallelic variants in CACNA1A have previously been reported in nine individuals (four families) presenting with epilepsy and cognitive impairments of variable severity and age-of-onset. Here, we describe a child who presented at 6 months of age with drug-resistant epilepsy and developmental delay. At 10 years of age, she has profound impairments in motor function and communication. MRI was initially unremarkable, but progressed to severe cerebellar atrophy by age 3 years. Next Generation Sequencing and panel analysis identified a maternally inherited truncating variant c.2042_2043delAG, p.(Gln681ArgfsTer100) and paternally inherited missense variant c.1693G>A, p.(Glu565Lys). In contrast to previously reported biallelic cases, parents carrying these monoallelic variants did not display clear signs of a CACNA1A-associated syndrome. In conclusion, we provide further evidence that biallelic CACNA1A variants can cause a severe epileptic and developmental encephalopathy with progressive cerebellar atrophy, and highlight complexities of genetic counseling in such situations.
摘要：
先前已经报道了CACNA1A的双等位基因变体在9个个体(4个家庭)中表现出不同严重程度和发病年龄的癫痫和认知障碍。这里,我们描述了一个在6月龄时出现耐药癫痫和发育迟缓的儿童.在10岁的时候，她有严重的运动功能和沟通障碍。MRI最初并不显著,但在3岁时发展为严重的小脑萎缩。下一代测序和小组分析确定了母系遗传的截短变体c.2042_2043delAG，p.（Gln681ArgfsTer100）和父系遗传错义变体c.1693G>A，p.（Glu565Lys）。与以前报道的双等位基因病例相比，携带这些单等位基因变异体的父母未显示出CACNA1A相关综合征的明确征象.总之,我们提供进一步的证据表明双等位基因CACNA1A变异体可引起严重的癫痫和发育性脑病伴进行性小脑萎缩,并强调在这种情况下遗传咨询的复杂性。
