Epilepsy Clinic, Hospital Sírio-Libanês,, Department of Neurology, University of São Paulo School of Medicine.
Department of Neurology, University of São Paulo School of Medicine.
Epileptic Disord. 2020 Jun 1;22(3):317-322. doi: 10.1684/epd.2020.1166.
ATP6V1B2 encodes a subunit of the lysosomal transmembrane proton pump necessary for adequate functioning of several acid hydrolases. De novo monoallelic variants of this gene have been associated with two distinct phenotypes: Zimmermann-Laband syndrome 2 (ZLS2), an intellectual deficiency/multiple malformation syndrome, and dominant deafness onychodystrophy (DDOD), a multiple malformation syndrome without cognitive involvement. Epilepsy is not observed in DDOD, is variably present in ZLS2, but is a common feature in Zimmermann-Laband syndrome 1 (ZLS1) (caused by monoallelic pathogenic variants in KCNH1) and Zimmermann-Laband syndrome-like (ZLSL) (associated with KCNK4 variants). Herein, we report a case of an infant with severe epileptic encephalopathy with microcephaly and profound developmental delay, associated with a novel de novo loss-of-function variant in ATP6V1B2, diagnosed by whole-exome sequencing. This finding expands the spectrum of ATP6V1B2-associated disorders and adds ATP6V1B2 as a new member for the growing list of early-onset epileptic encephalopathy genes. [Published with video sequence].
ATP6V1B2 编码溶酶体跨膜质子泵的亚基，该亚基对于几种酸性水解酶的正常功能是必需的。该基因的从头单等位基因变异与两种不同的表型有关：Zimmermann-Laband 综合征 2（ZLS2），一种智力缺陷/多发畸形综合征，以及显性耳聋甲营养不良（DDOD），一种无认知受累的多发畸形综合征。癫痫在 DDOD 中不观察到，在 ZLS2 中存在可变，但在 Zimmermann-Laband 综合征 1（ZLS1）（由 KCNH1 的单等位基因致病性变异引起）和 Zimmermann-Laband 综合征样（ZLSL）（与 KCNK4 变异相关）中是常见特征。在此，我们报告了一例伴有小头畸形和严重发育迟缓的婴儿严重癫痫性脑病病例，该病例与 ATP6V1B2 中的新型从头失活变异相关，通过全外显子组测序进行诊断。这一发现扩展了 ATP6V1B2 相关疾病的范围，并将 ATP6V1B2 作为新兴的早发性癫痫脑病基因列表中的新成员。[伴有视频序列发表]。
