Department of Neuromuscular Disorders, UCL Institute of Neurology, Queen Square, London WC1N 3BG, United Kingdom; Unit of Child Neurology and Psychiatry, Department of Human Pathology of the Adult and Developmental Age "Gaetano Barresi", University of Messina, Via C. Valeria 1, 98125 Messina, Italy.
Department of Neuromuscular Disorders, UCL Institute of Neurology, Queen Square, London WC1N 3BG, United Kingdom.
Brain Dev. 2023 Nov;45(10):588-596. doi: 10.1016/j.braindev.2023.07.004. Epub 2023 Aug 25.
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.
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).
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.
ATP6V1B2（ATP 酶，H+转运，溶酶体 VI 亚基 B，同种型 2）编码一种普遍存在的跨膜溶酶体质子泵的亚基，该亚基参与细胞内细胞器的酸化和多种其他细胞功能。ATP6V1B2 中的变体与一组异质性的多系统疾病有关，这些疾病有时与可变的神经受累有关。然而，由于报道的病例数量较少，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。
我们在此报告了一例 18 岁的西西里男性患者，患有全面发育迟缓、骨骼异常和伴有 Lennox-Gastaut 综合征（LGS）的癫痫性脑病，外显子组测序确定了 ATP6V1B2 中的一种新的从头变异（NM_001693.4：c.973G>C，p.Gly325Arg）。
我们的报告提供了将发育性癫痫性脑病（DEE）纳入 ATP6V1B2 相关疾病连续体组的新见解，扩展了与这些疾病相关的表型和分子谱。
