ArticleAmerican journal of human genetics2012
Mutations in DDHD2, encoding an intracellular phospholipase A(1), cause a recessive form of complex hereditary spastic paraplegia.
Article in American journal of human genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers, 2 of them syntheses that pooled it.
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Who cites it
109 citing papers in PubMed, 2 syntheses or guidelines pooled it, 182 citations in OpenAlex.
- Genotype-phenotype associations in hereditary spastic paraplegia: a systematic review and meta-analysis on 13,570 patients.Journal of neurology · 2021Pooled it
- Common genetic risk variants identified in the SPARK cohort support DDHD2 as a candidate risk gene for autism.Translational psychiatry · 2020Pooled it
- Neurons run on fat.npj metabolic health and disease · 2026Article
- Implications of mitochondrial phosphatidylethanolamine in neuronal health and neurodegeneration.Neural regeneration research · 2026Article
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- DDHD2 possesses both lipase and transacylase capacities that remodel triglyceride acyl chains.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- DDHD2 provides a flux of saturated fatty acids for neuronal energy and function.Nature metabolism · 2025Article
- DDHD2 possesses both lipase and transacylase capacities that remodel triglyceride acyl chains.bioRxiv : the preprint server for biology · 2025Article
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- Essential Biology of Lipid Droplets.Annual review of biochemistry · 2025Review
- Strabismus in Genetic Syndromes: A Review.Clinical & experimental ophthalmology · 2025Review
49 more citing papers are in PubMed but not listed here.
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41 authors at 6 institutions in 4 countries.
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Abstract
We report on four families affected by a clinical presentation of complex hereditary spastic paraplegia (HSP) due to recessive mutations in DDHD2, encoding one of the three mammalian intracellular phospholipases A(1) (iPLA(1)). The core phenotype of this HSP syndrome consists of very early-onset (<2 years) spastic paraplegia, intellectual disability, and a specific pattern of brain abnormalities on cerebral imaging. An essential role for DDHD2 in the human CNS, and perhaps more specifically in synaptic functioning, is supported by a reduced number of active zones at synaptic terminals in Ddhd-knockdown Drosophila models. All identified mutations affect the protein's DDHD domain, which is vital for its phospholipase activity. In line with the function of DDHD2 in lipid metabolism and its role in the CNS, an abnormal lipid peak indicating accumulation of lipids was detected with cerebral magnetic resonance spectroscopy, which provides an applicable diagnostic biomarker that can distinguish the DDHD2 phenotype from other complex HSP phenotypes. We show that mutations in DDHD2 cause a specific complex HSP subtype (SPG54), thereby linking a member of the PLA(1) family to human neurologic disease.
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