Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.4/1596
Título: Gain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome
Autor: Sousa, SB
Jenkins, D
Chanudet, E
Tasseva, G
Ishida, M
Anderson, G
Docker, J
Ryten, M
Sá, J
Saraiva, JM
Barnicoat, A
Scott, R
Calder, A
Wattanasirichaigoon, D
Chrzanowska, K
Simandlová, M
Van Maldergem, L
Stanier, P
Beales, PL
Vance, JE
Moore, GE
Palavras-chave: Anomalias Congénitas Múltiplas
Deficiência Intelectual
Transferases de Grupos Nitrogenados
Fosfatidilserinas
Data: 2013
Editora: Nature
Citação: Nat Genet. 2013 Nov 17. doi: 10.1038/ng.2829. [Epub ahead of print]
Resumo: 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.
Peer review: yes
URI: http://hdl.handle.net/10400.4/1596
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