1. ABHD16A deficiency causes a complicated form of hereditary spastic paraplegia associated with intellectual disability and cerebral anomalies.
- Author
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Lemire G, Ito YA, Marshall AE, Chrestian N, Stanley V, Brady L, Tarnopolsky M, Curry CJ, Hartley T, Mears W, Derksen A, Rioux N, Laflamme N, Hutchison HT, Pais LS, Zaki MS, Sultan T, Dane AD, Gleeson JG, Vaz FM, Kernohan KD, Bernard G, and Boycott KM
- Subjects
- Adolescent, Adult, Cerebral Palsy etiology, Cerebral Palsy metabolism, Child, Child, Preschool, Cohort Studies, Female, Humans, Intellectual Disability etiology, Intellectual Disability metabolism, Leukoencephalopathies etiology, Leukoencephalopathies metabolism, Male, Monoacylglycerol Lipases deficiency, Pedigree, Phenotype, Spastic Paraplegia, Hereditary etiology, Spastic Paraplegia, Hereditary metabolism, Young Adult, Cerebral Palsy pathology, Intellectual Disability pathology, Leukoencephalopathies pathology, Monoacylglycerol Lipases genetics, Mutation, Spastic Paraplegia, Hereditary pathology
- Abstract
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., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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