Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON K1H 8L1, Canada; Broad Center for Mendelian Genomics, Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON K1H 8L1, Canada.
Am J Hum Genet. 2021 Oct 7;108(10):2017-2023. doi: 10.1016/j.ajhg.2021.09.005. Epub 2021 Sep 28.
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（酰基辅酶 A 水解酶结构域蛋白 16A，磷脂酶）编码大脑中主要的磷脂酰丝氨酸（PS）脂酶。PS 脂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重要作用的信号脂质。ABHD16A 尚未与人类疾病相关。在本报告中，我们介绍了来自六个无关家庭的 11 名受累个体的队列，他们携带 ABHD16A 的双等位基因有害变异，患有复杂形式的遗传性痉挛性截瘫（HSP）。受累个体表现出相似的表型，包括全面发育迟缓/智力残疾、影响上下肢的进行性痉挛，以及胼胝体和白质异常。对来自四名受累个体的成纤维细胞提取物进行的免疫印迹分析显示，与对照组相比，ABHD16A 蛋白水平极低或不存在。我们的发现将 ABHD16A 添加到不断增长的脂质基因列表中，这些基因的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。
