期刊
AMERICAN JOURNAL OF HUMAN GENETICS
卷 108, 期 10, 页码 2017-2023出版社
CELL PRESS
DOI: 10.1016/j.ajhg.2021.09.005
关键词
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资金
- Genome Canada
- Ontario Genomics Institute [OGI-147]
- Canadian Institutes of Health Research
- Ontario Research Fund
- Genome Alberta
- Genome British Columbia
- Genome Quebec
- Children's Hospital of Eastern Ontario Foundation
- Fondation Leucodystrophie
- Children's Hospital of Eastern Ontario
- CIHR fellowship award [MFE176616]
- CIHR Foundation [FDN-154279]
- Tier 1 Canada Research Chair in Rare Disease Precision Health
- Fonds de Recherche du Quebec -Sante' (FRQS) (2012-2016)
- FRQS (2022-2025)
- National Human Genome Research Institute
- National Eye Institute
- National Heart, Lung, and Blood Institute [UM1 HG008900]
- National Human Genome Research Institute [R01 HG009141]
ABHD16A encodes the major PS lipase in the brain and its variants may lead to a complicated form of hereditary spastic paraplegia. Patients exhibit global developmental delay, progressive limb spasticity, and brain anomalies. This study contributes to understanding the molecular mechanisms of the condition.
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.
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