Gain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome
| العنوان: | Gain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome |
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| المؤلفون: | Mina Ryten, Sérgio B. Sousa, Richard H Scott, Estelle Chanudet, Glenn Anderson, Lionel Van Maldergem, Dagan Jenkins, Philip L. Beales, Krystyna H. Chrzanowska, James Docker, Jorge M. Saraiva, Philip Stanier, Gudrun E. Moore, Miho Ishida, Angela Barnicoat, Joaquim Sá, Martina Simandlova, Duangrurdee Wattanasirichaigoon, Guergana Tasseva, Jean E. Vance, Alistair Calder |
| المصدر: | Nature Genetics. 46:70-76 |
| بيانات النشر: | Springer Science and Business Media LLC, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Male, Fosfatidilserinas, Embryo, Nonmammalian, Adolescent, Nitrogenous Group Transferases, Molecular Sequence Data, Dwarfism, Phosphatidylserines, Biology, medicine.disease_cause, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Genetics, medicine, Animals, Humans, Missense mutation, Abnormalities, Multiple, Child, Gene, Cells, Cultured, Zebrafish, 030304 developmental biology, Transferases de Grupos Nitrogenados, Phosphatidylethanolamine, 0303 health sciences, Mutation, Deficiência Intelectual, Syndrome, Phosphatidylserine, Fibroblasts, Hyperostosis, medicine.disease, 3. Good health, chemistry, Craniotubular Hyperostosis, Female, Anomalias Congénitas Múltiplas, 030217 neurology & neurosurgery, Cutis laxa |
| الوصف: | Lenz-Majewski syndrome (LMS) is a syndrome of intellectual disability and multiple congenital anomalies that features generalized craniotubular hyperostosis. By using whole-exome sequencing and selecting variants consistent with the predicted dominant de novo etiology of LMS, we identified causative heterozygous missense mutations in PTDSS1, which encodes phosphatidylserine synthase 1 (PSS1). PSS1 is one of two enzymes involved in the production of phosphatidylserine. Phosphatidylserine synthesis was increased in intact fibroblasts from affected individuals, and end-product inhibition of PSS1 by phosphatidylserine was markedly reduced. Therefore, these mutations cause a gain-of-function effect associated with regulatory dysfunction of PSS1. We have identified LMS as the first human disease, to our knowledge, caused by disrupted phosphatidylserine metabolism. Our results point to an unexplored link between phosphatidylserine synthesis and bone metabolism. |
| تدمد: | 1546-1718 1061-4036 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9095fc09a7d92cabf8a2a5dc6673d2d1Test https://doi.org/10.1038/ng.2829Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9095fc09a7d92cabf8a2a5dc6673d2d1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15461718 10614036 |
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