Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, 410008, Hunan, China.
Department of Pediatrics, Peking University First Hospital, Beijing, 100034, China.
Neurol Sci. 2019 Nov;40(11):2325-2331. doi: 10.1007/s10072-019-03979-0. Epub 2019 Jun 25.
Microtubule dynamics is crucial for neuronal function and survival. The disrupted function of microtubule dynamics would lead to neurodegenerative and neurodevelopmental disorders. Tubulin-specific chaperone D (TBCD) is one of five tubulin co-chaperones acted in assembly and disassembly dynamics of microtubule. The biallelic pathogenic variants of TBCD gene were reported to be associated with severe degenerative encephalopathy accompanied with seizures previously.
Compound heterozygous variants were identified in three patients from three families. The in silico prediction software and ACMG standards and guidelines proved the pathogenicity of the TBCD pathogenic variants. The clinical features of the three patients presented with mild neurodevelopmental manifestations including autism spectrum disorder (ASD) and occasional generalized tonic-clonic seizures (GTCSs) responding well to antiepileptic drugs.
Our research expanded the clinical spectrum of TBCD-related neurodevelopmental disease which contributed to understanding the genotype-phenotype correlations of the disease.
微管动力学对神经元的功能和存活至关重要。微管动力学功能的破坏会导致神经退行性和神经发育障碍。微管特异性伴侣 D（TBCD）是在微管组装和去组装动力学中起作用的五个微管共伴侣之一。先前已有报道，TBCD 基因的双等位致病性变体与伴有癫痫发作的严重退行性脑病有关。
从三个家系的 3 名患者中鉴定出复合杂合变异体。计算机预测软件和 ACMG 标准和指南证明了 TBCD 致病性变异体的致病性。这 3 名患者的临床特征表现为轻度神经发育表现，包括自闭症谱系障碍（ASD）和偶尔的全面强直阵挛发作（GTCS），抗癫痫药物治疗效果良好。
我们的研究扩展了 TBCD 相关神经发育疾病的临床谱，有助于理解该疾病的基因型-表型相关性。
