Department of Pediatrics, the First Affiliated Hospital of Fujian Medical University, Fuzhou 350005,China.
Department of Pediatrics, the First Affiliated Hospital of Fujian Medical University, Fuzhou 350005,China.
Epilepsy Res. 2022 May;182:106923. doi: 10.1016/j.eplepsyres.2022.106923. Epub 2022 Apr 8.
Disorders associated with mutations in the Tre2/Bub2/Cdc16 (TBC)1 domain family member 24 gene (TBC1D24) present a wide range of phenotypes, ranging from mild to fatal seizure diseases, non-syndromic deafness, and complex syndromes such as deafness, onychodystrophy, osteodystrophy, and mental retardation(DOOR syndrome). In this study, we introduce three siblings of a previously unreported Chinese family with familial infantile myoclonic epilepsy caused by a homozygous TBC1D24 mutation.
Genomic DNA was extracted from whole blood of the proband, his parents, and sisters. TBC1D24 exomes were sequenced by whole exome sequencing then analyzed by genetic analysis with Sanger sequencing validation. The patients were followed up for more than 20 years to summarize their clinical features.
Genetic analysis identified a homozygous TBC1D24 mutation (c.241_252del12) in the proband and his sisters. Prediction models suggest that the mutation leads to an alteration in the properties and structure of the TBC1D24 protein, especially in the folding direction of the loop region, which is likely to decrease protein activity. The patients manifested with early-onset myoclonic epilepsy, were prone to status epilepticus, and seizures only occurred during wakefulness. Imaging characteristics included cerebellar atrophy and abnormal cerebellar signals.
We report a pedigree case of infantile myoclonic epilepsy caused by a homozygous TBC1D24 mutation. Our long-term clinical follow-up not only enriches the clinical phenotype of the disease, but also provides a clinical experience for the early diagnosis and clinical treatment of the disease.
Tre2/Bub2/Cdc16（TBC）1 结构域家族成员 24 基因（TBC1D24）突变相关疾病表现出广泛的表型，从轻到重的疾病包括癫痫、非综合征性耳聋以及复杂综合征如耳聋、甲营养不良、骨营养不良和智力迟钝（DOOR 综合征）。在本研究中，我们介绍了一个先前未报道的中国家族的三个兄弟姐妹，他们患有由 TBC1D24 突变引起的家族性婴儿肌阵挛性癫痫。
从先证者、他的父母和姐妹的全血中提取基因组 DNA。通过全外显子组测序对 TBC1D24 外显子组进行测序，然后通过遗传分析结合 Sanger 测序验证进行分析。对患者进行了 20 多年的随访，以总结其临床特征。
遗传分析在先证者及其姐妹中发现了 TBC1D24 基因的纯合突变（c.241_252del12）。预测模型表明，该突变导致 TBC1D24 蛋白的性质和结构发生改变，特别是在环区的折叠方向上，这可能会降低蛋白质的活性。患者表现为早发性肌阵挛性癫痫，易发生癫痫持续状态，且发作仅发生在觉醒期间。影像学特征包括小脑萎缩和小脑信号异常。
我们报告了一个由 TBC1D24 基因纯合突变引起的婴儿肌阵挛性癫痫家系病例。我们的长期临床随访不仅丰富了该疾病的临床表型，还为疾病的早期诊断和临床治疗提供了临床经验。
