Pediatric Neurology, Neurogenetics and Neurobiology Unit and Laboratories, Neuroscience Department, A. Meyer Children's Hospital, University of Florence, Italy.
CRIMM, Centro di Ricerca e Innovazione per le Malattie Mieloproliferative, Azienda Ospedaliera Universitaria Careggi, Florence, Italy.
Am J Med Genet A. 2018 Dec;176(12):2808-2812. doi: 10.1002/ajmg.a.40503. Epub 2018 Aug 25.
We describe a mother and son with focal epilepsy, mild cognitive impairment, and pachygyria, which was parieto-occipital in the mother and with remarkable posterior greater than anterior severity in the son. Overall clinical manifestations, although overlapping in type, were likewise slightly more severe in the son. Using targeted resequencing through a gene panel for malformations of cortical development, we identified the c.655 T > A [p.(Trp219Arg)] novel missense variant in the LIS1 gene, segregating in the proband and in his mother. Western Blot analysis, qPCR gene expression and RT-PCR disclosed no significant differences between proband, his parents, and controls. Epilepsy and mild cognitive impairment can be the only clinical presentation of constitutional LIS1 mutations, which can therefore be inherited if the associated phenotype implies limited or no reproductive disadvantage. Parents of patients harboring LIS1 mutations should be assessed for their mutation carrier status.
我们描述了一位母亲和她的儿子，他们患有局灶性癫痫、轻度认知障碍和脑回宽大，母亲的病变位于顶枕叶，而儿子的病变则以后部重于前部为显著特征。尽管总体临床表现的类型重叠，但儿子的表现也略为严重。通过针对皮质发育畸形的基因panel 进行靶向重测序，我们在 LIS1 基因中发现了 c.655 T > A [p.(Trp219Arg)] 新型错义变异，该变异在先证者及其母亲中发生了遗传。Western Blot 分析、qPCR 基因表达和 RT-PCR 显示，先证者、其父母和对照组之间没有显著差异。如果相关表型暗示有限或没有生殖劣势，那么癫痫和轻度认知障碍可能是 LIS1 基因突变的唯一临床表现，因此这种基因突变可以遗传。携带 LIS1 基因突变的患者的父母应评估其突变携带者状态。
