■动力蛋白细胞质1重链1(DYNC1H1)基因的突变与皮质发育(MCD)的畸形有关,可能伴有中枢神经系统(CNS)表现。这里,我们介绍了一例携带DYNC1H1变异体的MCD患者,并回顾了相关文献以探讨基因型-表型关系.
■一个婴儿痉挛的女孩,未成功服用多种抗癫痫药物并发展为耐药性癫痫。14个月大的脑磁共振成像(MRI)显示厚型。4岁时,患者表现出严重的发育迟缓和智力低下。从头杂合突变(p。在DYNC1H1基因中鉴定出Arg292Trp)。搜索多个数据库,包括PubMed和Embase,截至2022年6月,使用搜索策略DYNC1H1AND[皮质发育或癫痫发作或智力或临床症状的畸形],从43项研究(包括本文提供的病例)中确定了129例患者.对这些病例的回顾显示,患有DYNC1H1相关MCD的患者有更高的癫痫风险(比值比[OR]=33.67,95%置信区间[CI]=11.59,97.84)和智力残疾/发育迟缓(OR=52.64,95%CI=16.27,170.38)。在编码蛋白质茎或微管结合结构域的区域中具有变体的患者具有最普遍的MCD(95%)。
■MCD,尤其是pachygyria,是DYNC1H1突变患者常见的神经发育障碍。文献检索显示,大多数(95%)在蛋白质茎或微管结合域中携带突变的患者表现出DYNC1H1相关的MCD,而在尾部结构域携带突变的患者中,近三分之二(63%)未显示MCD.具有DYNC1H1突变的患者可能由于MCD而经历中枢神经系统(CNS)表现。
UNASSIGNED: Mutations in the dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) gene are linked to malformations of cortical development (MCD), which may be accompanied by central nervous system (CNS) manifestations. Here, we present the
case of a patient with MCD harboring a variant of DYNC1H1 and review the relevant literature to explore genotype-phenotype relationships.
UNASSIGNED: A girl having infantile spasms, was unsuccessfully administered multiple antiseizure medications and developed drug-resistant epilepsy. Brain magnetic resonance imaging (MRI) at 14 months-of-age revealed pachygyria. At 4 years-of-age, the patient exhibited severe developmental delay and mental retardation. A de novo heterozygous mutation (p.Arg292Trp) in the DYNC1H1 gene was identified. A search of multiple databases, including PubMed and Embase, using the search strategy DYNC1H1 AND [malformations of cortical development OR seizure OR intellectual OR clinical symptoms] up to June 2022, identified 129 patients from 43 studies (including the
case presented herein). A review of these cases showed that patients with DYNC1H1-related MCD had higher risks of epilepsy (odds ratio [OR] = 33.67, 95% confidence interval [CI] = 11.59, 97.84) and intellectual disability/developmental delay (OR = 52.64, 95% CI = 16.27, 170.38). Patients with the variants in the regions encoding the protein stalk or microtubule-binding domain had the most prevalence of MCD (95%).
UNASSIGNED: MCD, particularly pachygyria, is a common neurodevelopmental disorder in patients with DYNC1H1 mutations. Literature searches reveales that most (95%) patients who carried mutations in the protein stalk or microtubule binding domains exhibited DYNC1H1-related MCD, whereas almost two-thirds of patients (63%) who carried mutations in the tail domain did not display MCD. Patients with DYNC1H1 mutations may experience central nervous system (CNS) manifestations due to MCD.