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Gain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome

2013Journal article Open access
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dc.contributor.authorSousa, SB
dc.contributor.authorJenkins, D
dc.contributor.authorChanudet, E
dc.contributor.authorTasseva, G
dc.contributor.authorIshida, M
dc.contributor.authorAnderson, G
dc.contributor.authorDocker, J
dc.contributor.authorRyten, M
dc.contributor.authorSá, J
dc.contributor.authorSaraiva, JM
dc.contributor.authorBarnicoat, A
dc.contributor.authorScott, R
dc.contributor.authorCalder, A
dc.contributor.authorWattanasirichaigoon, D
dc.contributor.authorChrzanowska, K
dc.contributor.authorSimandlová, M
dc.contributor.authorVan Maldergem, L
dc.contributor.authorStanier, P
dc.contributor.authorBeales, PL
dc.contributor.authorVance, JE
dc.contributor.authorMoore, GE
dc.date.accessioned2013-11-20T14:45:09Z
dc.date.available2013-11-20T14:45:09Z
dc.date.issued2013
dc.description.abstractLenz-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.por
dc.identifier.citationNat Genet. 2013 Nov 17. doi: 10.1038/ng.2829. [Epub ahead of print]por
dc.identifier.urihttp://hdl.handle.net/10400.4/1596
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherNaturepor
dc.subjectAnomalias Congénitas Múltiplaspor
dc.subjectDeficiência Intelectualpor
dc.subjectTransferases de Grupos Nitrogenadospor
dc.subjectFosfatidilserinaspor
dc.titleGain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndromepor
dc.typejournal article
dspace.entity.typePublication
rcaap.rightsopenAccesspor
rcaap.typearticlepor

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