Gain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome
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...
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th-mahidol.335032018-11-09T09:01:06Z Gain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome Sérgio B. Sousa Dagan Jenkins Estelle Chanudet Guergana Tasseva Miho Ishida Glenn Anderson James Docker Mina Ryten Joaquim Sa Jorge M. Saraiva Angela Barnicoat Richard Scott Alistair Calder Duangrurdee Wattanasirichaigoon Krystyna Chrzanowska Martina Simandlová Lionel Van Maldergem Philip Stanier Philip L. Beales Jean E. Vance Gudrun E. Moore UCL Institute of Child Health Centro Hospitalar e Universitario de Coimbra University of Alberta UCL UCL Institute of Neurology Universidade de Coimbra, Faculdade de Medicina Mahidol University Instytut Pomnik-Centrum Zdrowia Dziecka Fakultni Nemocnice v Motole Universite de Franche-Comte Biochemistry, Genetics and Molecular Biology 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. © 2014 Nature America, Inc. 2018-11-09T02:01:06Z 2018-11-09T02:01:06Z 2014-01-01 Article Nature Genetics. Vol.46, No.1 (2014), 70-76 10.1038/ng.2829 15461718 10614036 2-s2.0-84891373792 https://repository.li.mahidol.ac.th/handle/123456789/33503 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84891373792&origin=inward |
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Biochemistry, Genetics and Molecular Biology Sérgio B. Sousa Dagan Jenkins Estelle Chanudet Guergana Tasseva Miho Ishida Glenn Anderson James Docker Mina Ryten Joaquim Sa Jorge M. Saraiva Angela Barnicoat Richard Scott Alistair Calder Duangrurdee Wattanasirichaigoon Krystyna Chrzanowska Martina Simandlová Lionel Van Maldergem Philip Stanier Philip L. Beales Jean E. Vance Gudrun E. Moore Gain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome |
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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. © 2014 Nature America, Inc. |
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UCL Institute of Child Health |
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UCL Institute of Child Health Sérgio B. Sousa Dagan Jenkins Estelle Chanudet Guergana Tasseva Miho Ishida Glenn Anderson James Docker Mina Ryten Joaquim Sa Jorge M. Saraiva Angela Barnicoat Richard Scott Alistair Calder Duangrurdee Wattanasirichaigoon Krystyna Chrzanowska Martina Simandlová Lionel Van Maldergem Philip Stanier Philip L. Beales Jean E. Vance Gudrun E. Moore |
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Article |
author |
Sérgio B. Sousa Dagan Jenkins Estelle Chanudet Guergana Tasseva Miho Ishida Glenn Anderson James Docker Mina Ryten Joaquim Sa Jorge M. Saraiva Angela Barnicoat Richard Scott Alistair Calder Duangrurdee Wattanasirichaigoon Krystyna Chrzanowska Martina Simandlová Lionel Van Maldergem Philip Stanier Philip L. Beales Jean E. Vance Gudrun E. Moore |
author_sort |
Sérgio B. Sousa |
title |
Gain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome |
title_short |
Gain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome |
title_full |
Gain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome |
title_fullStr |
Gain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome |
title_full_unstemmed |
Gain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome |
title_sort |
gain-of-function mutations in the phosphatidylserine synthase 1 (ptdss1) gene cause lenz-majewski syndrome |
publishDate |
2018 |
url |
https://repository.li.mahidol.ac.th/handle/123456789/33503 |
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1763498220906872832 |