ArticleAmerican journal of human genetics2007
Lethal contractural syndrome type 3 (LCCS3) is caused by a mutation in PIP5K1C, which encodes PIPKI gamma of the phophatidylinsitol pathway.
Article in American journal of human genetics, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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62 citing papers in PubMed, 108 citations in OpenAlex.
- From lipid dynamics to precision predictions: A new approach methodology for precision modeling of phosphoinositide signaling.Journal of precision medicine (Amsterdam, Netherlands) · 2026Article
- PIP4K attenuates PIP5K lipid kinase activity by disrupting membrane-mediated dimerization.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- A Ciliary Phosphoinositide Pathway Regulates the Dosage of Polycystins in Primary Cilia.Journal of the American Society of Nephrology : JASN · 2026Article
- A phosphoinositide switch from PI(4,5)PScience advances · 2025Article
- PIP4K attenuates PIP5K lipid kinase activity by disrupting membrane-mediated dimerization.bioRxiv : the preprint server for biology · 2025Article
- PIPKIγ promotes non-homologous end joining through LIG4 to enhance radiotherapy resistance in triple-negative breast cancer.Cell death & disease · 2025Article
- Genetic Basis of Motor Neuron Diseases: Insights, Clinical Management, and Future Directions.International journal of molecular sciences · 2025Review
- The role of CSNK1A1 and its de novo mutations in infantile spasms syndrome.Human molecular genetics · 2025Article
- Integration of transcriptomics and long-read genomics prioritizes structural variants in rare disease.Genome research · 2025Article
- Article
- Phosphoinositide Metabolism: Biochemistry, Physiology and Genetic Disorders.Journal of inherited metabolic disease · 2025Review
- Regulation of yeast polarized exocytosis by phosphoinositide lipids.Cellular and molecular life sciences : CMLS · 2024Review
- Review
- Temporal involvement of phosphatidylinositol 4-phosphate 5-kinase γ in differentiation of Z-bands and myofilament bundles as well as intercalated discs in mouse heart at mid-gestation.Journal of anatomy · 2024Article
- Integration of transcriptomics and long-read genomics prioritizes structural variants in rare disease.medRxiv : the preprint server for health sciences · 2024Article
- Novel PIP5K1C variant identified in a Chinese pedigree with lethal congenital contractural syndrome 3.BMC pediatrics · 2024Article
- Pip5k1c expression in osteocytes regulates bone remodeling in mice.Journal of orthopaedic translation · 2024Article
- Role of lipids in the control of autophagy and primary cilium signaling in neurons.Neural regeneration research · 2024Review
- The Silencing ofInternational journal of molecular sciences · 2024Article
- Identification and Analysis of the Expression of theInternational journal of molecular sciences · 2023Article
2 more citing papers are in PubMed but not listed here.
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8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lethal congenital contractural syndrome (LCCS) is a severe form of arthrogryposis. To date, two autosomal recessive forms of the disease (LCCS and LCCS2) have been described and mapped to chromosomes 9q34 and 12q13, respectively. We now describe a third LCCS phenotype (LCCS3)--similar to LCCS2 yet without neurogenic bladder. Using 10K single-nucleotide-polymorphism arrays, we mapped the disease-associated gene to 8.8 Mb on chromosome 19p13. Further analysis using microsatallite markers narrowed the locus to a 3.4-Mb region harboring 120 genes. Of these genes, 30 candidates were sequenced, which identified a single homozygous mutation in PIP5K1C. PIP5K1C encodes phosphatidylinositol-4-phosphate 5-kinase, type I, gamma (PIPKI gamma ), an enzyme that phophorylates phosphatidylinositol 4-phosphate to generate phosphatidylinositol-4,5-bisphosphate (PIP(2)). We demonstrate that the mutation causes substitution of aspartic acid with asparagine at amino acid 253 (D253N), abrogating the kinase activity of PIPKI gamma . Thus, a defect in the phosphatidylinositol pathway leading to a decrease in synthesis of PIP(2), a molecule active in endocytosis of synaptic vesicle proteins, culminates in lethal congenital arthrogryposis.
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