ABHD16A (abhydrolase domain-containing protein 16A, phospholipase) encodes the major phosphatidylserine (PS) lipase in the brain. PS lipase synthesizes lysophosphatidylserine, an important signaling lipid that functions in the mammalian central nervous system. ABHD16A has not yet been associated with a human disease. In this report, we present a cohort of 11 affected individuals from six unrelated families with a complicated form of hereditary spastic paraplegia (HSP) who carry bi-allelic deleterious variants in ABHD16A. Affected individuals present with a similar phenotype consisting of global developmental delay/intellectual disability, progressive spasticity affecting the upper and lower limbs, and corpus callosum and white matter anomalies. Immunoblot analysis on extracts from fibroblasts from four affected individuals demonstrated little to no ABHD16A protein levels compared to controls. Our findings add ABHD16A to the growing list of lipid genes in which dysregulation can cause complicated forms of HSP and begin to describe the molecular etiology of this condition.

ABHD16A（含有脱氢酶结构域的蛋白 16A，磷脂酶）编码大脑中的主要磷脂酰丝氨酸 (PS) 脂肪酶。PS 脂肪酶合成溶血磷脂酰丝氨酸，这是一种在哺乳动物中枢神经系统中起作用的重要信号脂质。ABHD16A尚未与人类疾病相关联。在本报告中，我们介绍了来自 6 个无关家庭的 11 名受影响个体，这些家庭患有复杂形式的遗传性痉挛性截瘫 (HSP)，他们在ABHD16A中携带双等位基因有害变异。受影响的个体表现出相似的表型，包括整体发育迟缓/智力残疾、影响上肢和下肢的进行性痉挛以及胼胝体和白质异常。对来自四个受影响个体的成纤维细胞提取物的免疫印迹分析表明，与对照组相比，ABHD16A 蛋白水平几乎没有或没有。我们的研究结果将ABHD16A添加到越来越多的脂质基因列表中，其中失调可导致复杂形式的 HSP，并开始描述这种情况的分子病因。