Severe neurodevelopmental disorder with intractable seizures due to a novel SLC1A4 homozygous variant
Severe neurodevelopmental disorder with intractable seizures due to a novel SLC1A4 homozygous variant
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DOI：
10.1016/j.ejmg.2021.104263
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发表时间：
2021-06-28
影响因子：
1.9
通讯作者：
Seeman, Pavel
中科院分区：
文献类型：
--
作者：
Sedlackova, Lucie;Lassuthova, Petra;Seeman, Pavel
简介：SLC1A4基因中的双等位基因变体迄今已被确定为伴有或不伴有癫痫的神经发育障碍的非常罕见的原因，并且几乎仅在德系犹太人群体中描述。患者和方法：在这里，我们介绍了一名患有小头畸形、严重的全面发育迟缓和顽固性癫痫发作的捷克患者，尽管获得了临床经验和标准诊断方法，包括使用癫痫靶向NGS基因组进行检查，但其病情仍未得到诊断。结果：全外显子序列分析发现一个新的突变体NM_003038.4：c.1370G > A p。（Arg457Gln），之后在双亲中进行桑格测序，证实了该变体的双等位基因起源。在同一密码子中的一个变体，但具有不同的氨基酸交换，先前在一个具有非常相似的表型的患者中描述过，然而，没有癫痫。结论：我们的数据表明，SLC1A4基因应考虑在严重的，早发性神经发育障碍伴癫痫患者的诊断，并鼓励通过靶向NGS基因面板或全外显子组测序SLC1A4基因变异的分析。
Introduction: Biallelic variants in the SLC1A4 gene have been so far identified as a very rare cause of neurodevelopmental disorders with or without epilepsy and almost exclusively described in the Ashkenazi-Jewish population. Patients and methods: Here we present Czech patient with microcephaly, severe global developmental delay and intractable seizures whose condition remained undiagnosed despite access to clinical experience and standard diagnostic methods including examination with an epilepsy targeted NGS gene panel. Results: Whole exome sequencing revealed a novel variant NM_003038.4:c.1370G > A p.(Arg457Gln) of the SLC1A4 gene in a homozygous state in the patient, and afterwards Sanger sequencing in both parents confirmed the biallelic origin of the variant. A variant in the same codon, but with a different amino acid exchange, was described previously in a patient that had a very similar phenotype, however, without epilepsy. Conclusion: Our data suggest that the SLC1A4 gene should be considered in the diagnosis of patients with severe, early onset neurodevelopmental impairment with epilepsy and encourage the analysis of SLC1A4 gene variants via targeted NGS gene panel or whole exome sequencing.