Background

ATP6V1B2 (ATPase, H+ transporting, lysosomal VI subunit B, isoform 2) encodes for a subunit of a ubiquitous transmembrane lysosomal proton pump, implicated in the acidification of intracellular organelles and in several additional cellular functions. Variants in ATP6V1B2 have been related to a heterogeneous group of multisystemic disorders sometimes associated with variable neurological involvement. However, our knowledge of genotype-phenotype correlations and the neurological spectrum of ATP6V1B2-related disorders remain limited due to the few numbers of reported cases.

Case study

We hereby report the case of an 18-year-old male Sicilian patient affected by a global developmental delay, skeletal abnormalities, and epileptic encephalopathy featuring Lennox-Gastaut syndrome (LGS), in which exome sequencing led to the identification of a novel de novo variant in ATP6V1B2 (NM_001693.4: c.973G > C, p.Gly325Arg).

Conclusions

Our report provides new insights on the inclusion of developmental epileptic encephalopathies (DEEs) within the continuum group of ATP6V1B2-related disorders, expanding the phenotypic and molecular spectrum associated with these conditions.

中文翻译：

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以 Lennox-Gastaut 综合征为特征的 ATP6V1B2 相关疾病：基于病例的概述

背景

ATP6V1B2 （ATP 酶，H+ 转运，溶酶体 VI 亚基 B，亚型 2）编码普遍存在的跨膜溶酶体质子泵的亚基，与细胞内细胞器的酸化和一些其他细胞功能有关。ATP6V1B2的变异与一组异质的多系统疾病有关，有时与不同的神经系统受累有关。然而，由于报告的病例数量很少，我们对ATP6V1B2相关疾病的基因型-表型相关性和神经学谱的了解仍然有限。

案例分析

我们在此报告一名 18 岁西西里男性患者的病例，该患者患有整体发育迟缓、骨骼异常和以 Lennox-Gastaut 综合征 (LGS) 为特征的癫痫性脑病，其中外显子组测序导致鉴定出一种新的新基因ATP6V1B2中的变体（NM_001693.4：c.973G > C，p.Gly325Arg）。

结论

我们的报告提供了关于将发育性癫痫性脑病 (DEE) 纳入ATP6V1B2相关疾病连续组的新见解，扩大了与这些疾病相关的表型和分子谱。