New SMS mutation leads to a striking reduction in spermine synthase protein function and a severe form of Snyder-Robinson XLMR syndrome
Gustavo Alencastro 1, Diane E. McCloskey 2, Susana E. Kliemann 3, Carlos M. Maranduba 1, Anthony E. Pegg 4, Xiaojing Wang 4, Débora R. Bertola 5, Charles E. Schwartz 6, Maria Rita Passos-Bueno 7 and Andréa L. Sertié 7*
1 Centro de Estudos do Genoma Humano, Instituto de Bioc, Brazil
2 Department of Cellular and Molecular Pathology, Penn State University College of Medicine, Hershey., United States
3 Associação Cruz Verde, São Paulo, Brazil
4 Department of Cellular and Molecular Pathology, Penn State University College of Medicine, Hershey, United States
5 Instituto da Criança do Hospital das Clínicas, Faculdade de Medicina, USP, São, United States
6 Greenwood Genetic Center, J.C. Self Research Institute of Human Genetics, Greenwood, United States
7 Centro de Estudos do Genoma Humano, Departamento de Genética e Biologia Evolutiva, Instituto, Brazil
* To whom correspondence should be addressed. E-mail: asertie{at}hotmail.com.
Accepted 12 May 2008
 | Abstract |
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We report the identification of a novel mutation at a highly conserved residue within the N-terminal region of spermine synthase (SMS) in a second family with Snyder-Robinson X-linked mental retardation syndrome (OMIM #309583). This missense mutation, p.G56S, greatly reduces SMS activity and leads to severe epilepsy and cognitive impairment. Our findings contribute to a better delineation and expansion of the clinical spectrum of Snyder-Robinson syndrome, support the important role of the N-terminus in the function of the SMS protein, and provide further evidence for the importance of SMS activity in the development of intellectual processing and other aspects of human development.
