spermine synthase

Summary

Summary: An enzyme that catalyzes the transfer of the propylamine moiety from 5'-deoxy-5'-S-(3-methylthiopropylamine)sulfonium adenosine to spermidine in the biosynthesis of spermine. It has an acidic isoelectric point at pH 5.0. EC 2.5.1.22.

Top Publications

  1. de Alencastro G, McCloskey D, Kliemann S, Maranduba C, Pegg A, Wang X, et al. New SMS mutation leads to a striking reduction in spermine synthase protein function and a severe form of Snyder-Robinson X-linked recessive mental retardation syndrome. J Med Genet. 2008;45:539-43 pubmed publisher
    ..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)...
  2. Wang X, Levic S, Gratton M, Doyle K, Yamoah E, Pegg A. Spermine synthase deficiency leads to deafness and a profound sensitivity to alpha-difluoromethylornithine. J Biol Chem. 2009;284:930-7 pubmed publisher
    ..This defect was due to alteration in polyamine content due to the absence of spermine synthase, the product of the SpmS gene...
  3. Zhang Z, Norris J, Schwartz C, Alexov E. In silico and in vitro investigations of the mutability of disease-causing missense mutation sites in spermine synthase. PLoS ONE. 2011;6:e20373 pubmed publisher
    b>Spermine synthase (SMS) is a key enzyme controlling the concentration of spermidine and spermine in the cell...
  4. Pegg A, Michael A. Spermine synthase. Cell Mol Life Sci. 2010;67:113-21 pubmed publisher
    ..It is synthesized by spermine synthase, a highly specific aminopropyltransferase...
  5. Stefanelli C, Pignatti C, Tantini B, Fattori M, Stanic I, Mackintosh C, et al. Effect of polyamine depletion on caspase activation: a study with spermine synthase-deficient cells. Biochem J. 2001;355:199-206 pubmed
    ..These cells lack spermine synthase activity and thus provide a valuable model to study the role of spermine in cell processes...
  6. Boeddrich A, Burgtorf C, Roest Crollius H, Hennig S, Bernot A, Clark M, et al. Analysis of the spermine synthase gene region in Fugu rubripes, Tetraodon fluviatilis, and Danio rerio. Genomics. 1999;57:164-8 pubmed
    ..We have focused on the spermine synthase gene in human Xp22. 1...
  7. Zhang Z, Teng S, Wang L, Schwartz C, Alexov E. Computational analysis of missense mutations causing Snyder-Robinson syndrome. Hum Mutat. 2010;31:1043-9 pubmed publisher
    ..Specifically, the p.G56S mutation is predicted to greatly reduce the affinity of monomers to form a dimer, and therefore should have a dramatic effect on SMS function because dimerization is essential for SMS activity. ..
  8. Lorenz B, Francis F, Gempel K, Böddrich A, Josten M, Schmahl W, et al. Spermine deficiency in Gy mice caused by deletion of the spermine synthase gene. Hum Mol Genet. 1998;7:541-7 pubmed
    ..The human SMS (spermine synthase) gene maps approximately 39 kb upstream of PHEX and is transcribed in the same direction...
  9. Beppu T, Shirahata A, Takahashi N, Hosoda H, Samejima K. Specific depletion of spermidine and spermine in HTC cells treated with inhibitors of aminopropyltransferases. J Biochem. 1995;117:339-45 pubmed
    The effects of a potent spermidine synthase inhibitor, trans-4-methylcyclohexylamine (4MCHA), and a spermine synthase inhibitor, N-(3-aminopropyl)cyclohexylamine (APCHA), on polyamine biosynthesis and cell growth have been studied in rat ..

More Information

Publications62

  1. Shirahata A, Takahashi N, Beppu T, Hosoda H, Samejima K. Effects of inhibitors of spermidine synthase and spermine synthase on polyamine synthesis in rat tissues. Biochem Pharmacol. 1993;45:1897-903 pubmed
    ..APCHA), selectively and potently inhibited the activities of spermidine synthase and spermine synthase, respectively. They were subjected to in vivo studies using rats...
  2. Zhang Z, Norris J, Kalscheuer V, Wood T, Wang L, Schwartz C, et al. A Y328C missense mutation in spermine synthase causes a mild form of Snyder-Robinson syndrome. Hum Mol Genet. 2013;22:3789-97 pubmed publisher
    ..It is caused by a significant decrease or loss of spermine synthase (SMS) activity. Here, we report a new missense mutation, p.Y328C (c...
  3. Wu H, Min J, Zeng H, McCloskey D, Ikeguchi Y, Loppnau P, et al. Crystal structure of human spermine synthase: implications of substrate binding and catalytic mechanism. J Biol Chem. 2008;283:16135-46 pubmed publisher
    The crystal structures of two ternary complexes of human spermine synthase (EC 2.5.1.22), one with 5'-methylthioadenosine and spermidine and the other with 5'-methylthioadenosine and spermine, have been solved...
  4. Clay N, Nelson T. Arabidopsis thickvein mutation affects vein thickness and organ vascularization, and resides in a provascular cell-specific spermine synthase involved in vein definition and in polar auxin transport. Plant Physiol. 2005;138:767-77 pubmed
    ..The tkv mutation was found to reside in the ACL5 gene, which encodes a spermine synthase and whose expression is specific to provascular cells...
  5. Cason A, Ikeguchi Y, Skinner C, Wood T, Holden K, Lubs H, et al. X-linked spermine synthase gene (SMS) defect: the first polyamine deficiency syndrome. Eur J Hum Genet. 2003;11:937-44 pubmed
    ..We report the first polyamine deficiency syndrome caused by a defect in spermine synthase (SMS)...
  6. Grieff M, Whyte M, Thakker R, Mazzarella R. Sequence analysis of 139 kb in Xp22.1 containing spermine synthase and the 5' region of PEX. Genomics. 1997;44:227-31 pubmed
    ..In addition, we mapped and analyzed another gene 5' of PEX, spermine synthase (SpS), which encodes a ubiquitous enzyme of polyamine metabolism that may contribute to the pathophysiology ..
  7. He Y, Shimogori T, Kashiwagi K, Shirahata A, Igarashi K. Inhibition of cell growth by combination of alpha-difluoromethylornithine and an inhibitor of spermine synthase. J Biochem. 1995;117:824-9 pubmed
  8. Pegg A, Wang X, Schwartz C, McCloskey D. Spermine synthase activity affects the content of decarboxylated S-adenosylmethionine. Biochem J. 2011;433:139-44 pubmed publisher
    ..It was found that in mice lacking spermine synthase there was a large increase in dcAdoMet and that overexpression of spermine synthase reduced the amount of ..
  9. Zhang Z, Miteva M, Wang L, Alexov E. Analyzing effects of naturally occurring missense mutations. Comput Math Methods Med. 2012;2012:805827 pubmed publisher
    ..The paper provides several examples of the application of 3D structure-based methods to model the effects of protein stability and protein-protein interactions caused by missense mutations as well. ..
  10. Gonzalez M, Marco F, Minguet E, Carrasco Sorli P, Blázquez M, Carbonell J, et al. Perturbation of spermine synthase gene expression and transcript profiling provide new insights on the role of the tetraamine spermine in Arabidopsis defense against Pseudomonas viridiflava. Plant Physiol. 2011;156:2266-77 pubmed publisher
    ..of plant spermine levels on susceptibility to bacterial infection were evaluated in transgenic plants (35S::spermine synthase [SPMS]) that overexpressed the SPMS gene and accumulated spermine, as well as in spms mutants with low ..
  11. Meyer R, Henley C, Meyer M, Morgan P, McDonald A, Mills C, et al. Partial deletion of both the spermine synthase gene and the Pex gene in the X-linked hypophosphatemic, gyro (Gy) mouse. Genomics. 1998;48:289-95 pubmed
    ..Since the gene for spermine synthase is immediately upstream of the homologous human gene PEX, we compared the effects of the Gy and Hyp ..
  12. Hamasaki Katagiri N, Katagiri Y, Tabor C, Tabor H. Spermine is not essential for growth of Saccharomyces cerevisiae: identification of the SPE4 gene (spermine synthase) and characterization of a spe4 deletion mutant. Gene. 1998;210:195-201 pubmed
    ..In order to investigate the physiological roles of spermine, we identified the SPE4 gene, which codes for spermine synthase, on the right arm of chromosome XII of Saccharomyces cerevisiae and prepared a deletion mutant in this gene...
  13. Hanzawa Y, Takahashi T, Michael A, Burtin D, Long D, Pineiro M, et al. ACAULIS5, an Arabidopsis gene required for stem elongation, encodes a spermine synthase. EMBO J. 2000;19:4248-56 pubmed
    ..a protein that shares sequence similarity with the polyamine biosynthetic enzymes spermidine synthase and spermine synthase. Expression of the recombinant ACL5 protein in Escherichia coli showed that ACL5 possesses spermine synthase ..
  14. Mackintosh C, Pegg A. Effect of spermine synthase deficiency on polyamine biosynthesis and content in mice and embryonic fibroblasts, and the sensitivity of fibroblasts to 1,3-bis-(2-chloroethyl)-N-nitrosourea. Biochem J. 2000;351 Pt 2:439-47 pubmed
    ..mice, which have previously been described as having disruption of the phosphate-regulating Phex gene and a spermine synthase gene [Meyer, Henley, Meyer, Morgan, McDonald, Mills and Price (1998) Genomics, 48, 289-295; Lorenz, Francis, ..
  15. Nilsson J, Gritli Linde A, Heby O. Skin fibroblasts from spermine synthase-deficient hemizygous gyro male (Gy/Y) mice overproduce spermidine and exhibit increased resistance to oxidative stress but decreased resistance to UV irradiation. Biochem J. 2000;352 Pt 2:381-7 pubmed
    ..in Gy/Y mice have recently been attributed to the fact that the Gy deletion also includes the neighbouring spermine synthase gene, resulting in spermine deficiency...
  16. Fiori L, Turecki G. Genetic and epigenetic influences on expression of spermine synthase and spermine oxidase in suicide completers. Int J Neuropsychopharmacol. 2010;13:725-36 pubmed publisher
    Alterations in the levels of spermine synthase (SMS) and spermine oxidase (SMOX), two enzymes involved in polyamine metabolism, have previously been observed in brains of suicide completers...
  17. Schwartz C, Wang X, Stevenson R, Pegg A. Spermine synthase deficiency resulting in X-linked intellectual disability (Snyder-Robinson syndrome). Methods Mol Biol. 2011;720:437-45 pubmed publisher
    ..Polyamines, spermidine and spermine, are synthesized by two aminopropyltransferases, spermidine synthase and spermine synthase. Recently, mutations in the latter enzyme have been shown to be responsible for an X-linked intellectual ..
  18. Becerra Solano L, Butler J, Castañeda Cisneros G, McCloskey D, Wang X, Pegg A, et al. A missense mutation, p.V132G, in the X-linked spermine synthase gene (SMS) causes Snyder-Robinson syndrome. Am J Med Genet A. 2009;149A:328-35 pubmed publisher
    ..3-p22.12, and a G-to-A transition at point +5 of intron 4 of the spermine synthase gene, which caused truncation of the SMS protein and loss of enzyme activity, was identified in the original ..
  19. Ikeguchi Y, Mackintosh C, McCloskey D, Pegg A. Effect of spermine synthase on the sensitivity of cells to anti-tumour agents. Biochem J. 2003;373:885-92 pubmed
    ..established and experimental anti-tumour agents was examined, using paired cell lines that possess or lack spermine synthase. All spermine-synthase-deficient cells had no detectable spermine, and elevated spermidine, content...
  20. Ikeguchi Y, Wang X, McCloskey D, Coleman C, Nelson P, Hu G, et al. Characterization of transgenic mice with widespread overexpression of spermine synthase. Biochem J. 2004;381:701-7 pubmed
    A widespread increase in SpmS (spermine synthase) activity has been produced in transgenic mice using a construct in which the human SpmS cDNA was placed under the control of a composite CMV-IE (cytomegalovirus immediate early gene) ..
  21. Kesler S, Schwartz C, Stevenson R, Reiss A. The impact of spermine synthase (SMS) mutations on brain morphology. Neurogenetics. 2009;10:299-305 pubmed publisher
    Snyder-Robinson syndrome (SRS) is a form of X-linked mental retardation resulting from mutations in spermine synthase (SMS), which impact neurodevelopment and cognitive outcome...
  22. Maekawa S, Hibasami H, Uji Y, Nakashima K. Active transport and metabolic characteristics of polyamines in the rat lens. Biochim Biophys Acta. 1989;993:199-203 pubmed
    ..The polyamines in the lens are considered to be supplied form the surrounding intraocular fluid by an active transport system specific for polyamines. ..
  23. Fiori L, Bureau A, Labbe A, Croteau J, Noël S, Mérette C, et al. Global gene expression profiling of the polyamine system in suicide completers. Int J Neuropsychopharmacol. 2011;14:595-605 pubmed publisher
    ..Among these, altered expression of spermidine/spermine N1-acetyltransferase, spermine oxidase, and spermine synthase, has previously been observed in brains of suicide completers, while the remainder of the genes represent ..
  24. Ohtani M, Mizuno I, Kojima Y, Ishikawa Y, Sodeno M, Asakura Y, et al. Spermidine regulates insulin synthesis and cytoplasmic Ca(2+) in mouse beta-TC6 insulinoma cells. Cell Struct Funct. 2009;34:105-13 pubmed
    ..of the polyamines spermidine and spermine in pancreatic beta-cells, we examined the effect of spermidine and spermine synthase inhibitors, trans-4-methylcyclohexylamine (MCHA) and N-(3-aminopropyl)cyclohexylamine (APCHA), on cellular ..
  25. Bae H, Kim S, Kim M, Sicher R, Lary D, Strem M, et al. The drought response of Theobroma cacao (cacao) and the regulation of genes involved in polyamine biosynthesis by drought and other stresses. Plant Physiol Biochem. 2008;46:174-88 pubmed publisher
    ..TcADC), an S-adenosylmethionine decarboxylase (TcSAMDC), a spermidine synthase (TcSPDS), and a spermine synthase (TcSPMS)...
  26. Zhang Z, Zheng Y, Petukh M, PEGG A, Ikeguchi Y, Alexov E. Enhancing human spermine synthase activity by engineered mutations. PLoS Comput Biol. 2013;9:e1002924 pubmed publisher
    b>Spermine synthase (SMS) is an enzyme which function is to convert spermidine into spermine...
  27. Lakanen J, Coward J, Pegg A. alpha-Methyl polyamines: metabolically stable spermidine and spermine mimics capable of supporting growth in cells depleted of polyamines. J Med Chem. 1992;35:724-34 pubmed
    In order to assess the tolerance of the target enzyme spermine synthase for alpha-substituents on the aminopropyl moiety of the substrate spermidine, 1-methylspermidine (MeSpd, 2) was synthesized...
  28. Rivarola V, Balegno H. 2,4-Dichlorophenoxyacetic acid effects on polyamine biosynthesis. Toxicology. 1991;68:109-19 pubmed
    ..The present work examined the effects of 2,4-D on polyamine biosynthesis. The results suggest some possible mechanism of the herbicide's toxic effects on animal cells. ..
  29. Wang X, Ikeguchi Y, McCloskey D, Nelson P, Pegg A. Spermine synthesis is required for normal viability, growth, and fertility in the mouse. J Biol Chem. 2004;279:51370-5 pubmed
    ..Spermine is formed from spermidine by the action of spermine synthase, an aminopropyltransferase, whose gene (SpmS) is located on the X chromosome...
  30. Pegg A, Wechter R, Poulin R, Woster P, Coward J. Effect of S-adenosyl-1,12-diamino-3-thio-9-azadodecane, a multisubstrate adduct inhibitor of spermine synthase, on polyamine metabolism in mammalian cells. Biochemistry. 1989;28:8446-53 pubmed
    The effects of the potent spermine synthase inhibitor S-adenosyl-1,12-diamino-3-thio-9-azadodecane (AdoDatad) on polyamine biosynthesis have been studied in transformed mouse fibroblasts (SV 3T3 cells) and in mouse leukemia cells (L1210)...
  31. Holm I, Persson L, Pegg A, Heby O. Effects of S-adenosyl-1,8-diamino-3-thio-octane and S-methyl-5'-methylthioadenosine on polyamine synthesis in Ehrlich ascites-tumour cells. Biochem J. 1989;261:205-10 pubmed
    ..In the present work the spermidine synthase inhibitor S-adenosyl-1,8-diamino-3-thio-octane (AdoDATO) and the spermine synthase inhibitor S-methyl-5'-methylthioadenosine (MMTA) were used to evaluate the regulatory role of the individual ..
  32. Peng Y, Norris J, Schwartz C, Alexov E. Revealing the Effects of Missense Mutations Causing Snyder-Robinson Syndrome on the Stability and Dimerization of Spermine Synthase. Int J Mol Sci. 2016;17: pubmed publisher
    Missense mutations in spermine synthase (SpmSyn) protein have been shown to cause the Snyder-Robinson syndrome (SRS)...
  33. Levillain O, Ramos Molina B, Forcheron F, Peñafiel R. Expression and distribution of genes encoding for polyamine-metabolizing enzymes in the different zones of male and female mouse kidneys. Amino Acids. 2012;43:2153-63 pubmed publisher
    ..The biosynthetic genes, ornithine decarboxylase (ODC) and spermine synthase, were more expressed in the cortex, whereas the mRNAs of the catabolic genes spermine oxidase (SMO) and ..
  34. Rodríguez Kessler M, Delgado Sánchez P, Rodríguez Kessler G, Moriguchi T, Jiménez Bremont J. Genomic organization of plant aminopropyl transferases. Plant Physiol Biochem. 2010;48:574-90 pubmed publisher
    Aminopropyl transferases like spermidine synthase (SPDS; EC 2.5.1.16), spermine synthase and thermospermine synthase (SPMS, tSPMS; EC 2.5.1...
  35. Pegg A, Coward J. Effect of N-(n-butyl)-1,3-diaminopropane on polyamine metabolism, cell growth and sensitivity to chloroethylating agents. Biochem Pharmacol. 1993;46:717-24 pubmed
  36. Kuratomi G, Iwamoto K, Bundo M, Kusumi I, Kato N, Iwata N, et al. Aberrant DNA methylation associated with bipolar disorder identified from discordant monozygotic twins. Mol Psychiatry. 2008;13:429-41 pubmed
    ..Two regions, upstream regions of spermine synthase (SMS) and peptidylprolyl isomerase E-like (PPIEL) (CN265253), showed aberrant DNA methylation status in ..
  37. Janne J, Alhonen L, Pietilä M, Keinänen T. Genetic approaches to the cellular functions of polyamines in mammals. Eur J Biochem. 2004;271:877-94 pubmed
    ..Finally, the first reports of human diseases apparently caused by mutations or rearrangements of the genes involved in polyamine metabolism have appeared. ..
  38. Nagarajan S, Ganem B, Pegg A. Studies of non-metabolizable polyamines that support growth of SV-3T3 cells depleted of natural polyamines by exposure to alpha-difluoromethylornithine. Biochem J. 1988;254:373-8 pubmed
    ..It was found that none of the compounds were effective substrates for spermine synthase, and only one, namely 8,8-dimethylspermidine, was a substrate for spermidine/spermine N1-acetyltransferase...
  39. Peron A, Spaccini L, Norris J, Bova S, Selicorni A, Weber G, et al. Snyder-Robinson syndrome: a novel nonsense mutation in spermine synthase and expansion of the phenotype. Am J Med Genet A. 2013;161A:2316-20 pubmed publisher
    Snyder-Robinson syndrome is a rare form of X-linked intellectual disability caused by mutations in the spermine synthase (SMS) gene, and characterized by intellectual disability, thin habitus with diminished muscle mass, osteoporosis, ..
  40. Desforges B, Curmi P, Bounedjah O, Nakib S, Hamon L, De Bandt J, et al. An intercellular polyamine transfer via gap junctions regulates proliferation and response to stress in epithelial cells. Mol Biol Cell. 2013;24:1529-43 pubmed publisher
    ..Some putative in vivo consequences of polyamine-mediated intercellular interactions are also discussed regarding cancer invasiveness and tissue regeneration. ..
  41. Sagor G, Berberich T, Takahashi Y, Niitsu M, Kusano T. The polyamine spermine protects Arabidopsis from heat stress-induced damage by increasing expression of heat shock-related genes. Transgenic Res. 2013;22:595-605 pubmed publisher
    ..6) were detected proportionally with the levels of their respective transcripts upon HS. We propose that Spm increases the HS response at transcriptional and translational levels and protects host plants from HS-induced damage...
  42. Shirahata A, Morohohi T, Fukai M, Akatsu S, Samejima K. Putrescine or spermidine binding site of aminopropyltransferases and competitive inhibitors. Biochem Pharmacol. 1991;41:205-12 pubmed
    ..On the basis of the above-mentioned model, another modified one was proposed for spermine synthase, and several compounds mentioned model, another modified one was proposed for spermine synthase, and several ..
  43. Eloranta T, Khomutov A, Khomutov R, Hyvonen T. Aminooxy analogues of spermidine as inhibitors of spermine synthase and substrates of hepatic polyamine acetylating activity. J Biochem. 1990;108:593-8 pubmed
    ..Both compounds were good competitive inhibitors and poor substrates of spermine synthase, good substrates of cytosolic polyamine acetyltransferase, inactivators of S-adenosylmethionine ..
  44. Seiler N. Thirty years of polyamine-related approaches to cancer therapy. Retrospect and prospect. Part 1. Selective enzyme inhibitors. Curr Drug Targets. 2003;4:537-64 pubmed
    ..These approaches are the topic of the 2nd part of this overview. ..
  45. Pegg A, Nagarajan S, Naficy S, Ganem B. Role of unsaturated derivatives of spermidine as substrates for spermine synthase and in supporting growth of SV-3T3 cells. Biochem J. 1991;274 ( Pt 1):167-71 pubmed
    Synthetic unsaturated analogues of the natural polyamine were examined as possible substrates for spermine synthase and as replacements for spermidine in supporting the growth of SV-3T3 cells...
  46. Yao X, Li C, Zhang J, Lu C. ?-glutamyl Spermine Synthetase PauA2 as a potential target of antibiotic development against Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2012;56:5309-14 pubmed publisher
    ..In summary, this study reveals the importance of GPS in alleviation of polyamine toxicity when in excess, and it provides strong support to the feasibility of GPS as a molecular target for new antibiotic development. ..
  47. Wang X, Pegg A. Use of (Gyro) Gy and spermine synthase transgenic mice to study functions of spermine. Methods Mol Biol. 2011;720:159-70 pubmed publisher
    ..putrescine or spermidine (which also -prevent the production of spermine) is lethal, but male mice lacking spermine synthase (SpmS) due to a deletion of part of the X chromosome are viable on the B6C3H background...
  48. Sowell J, Norris J, Jones K, Schwartz C, Wood T. Diagnostic screening for spermine synthase deficiency by liquid chromatography tandem mass spectrometry. Clin Chim Acta. 2011;412:655-60 pubmed publisher
    ..The disorder is caused by a mutation in the spermine synthase (SMS) gene. The SMS gene encodes an enzyme involved in polyamine metabolism...
  49. Lopatin A, Shantz L, Mackintosh C, Nichols C, Pegg A. Modulation of potassium channels in the hearts of transgenic and mutant mice with altered polyamine biosynthesis. J Mol Cell Cardiol. 2000;32:2007-24 pubmed
    ..I(K1)and I(to)currents were also studied in myocytes from mutant Gyro (Gy) mice in which the spermine synthase gene is disrupted, leading to a complete loss of spermine...
  50. Shantz L, Holm I, Janne O, Pegg A. Regulation of S-adenosylmethionine decarboxylase activity by alterations in the intracellular polyamine content. Biochem J. 1992;288 ( Pt 2):511-8 pubmed
    ..DFMO treatment did not interfere with the expression of plasmids driven by the RSV promoter. These results suggest that low spermidine levels interfere with the replication of plasmids containing the SV40 origin of replication. ..
  51. Baillon J, Mamont P, Wagner J, Gerhart F, Lux P. Fluorinated analogues of spermidine as substrates of spermine synthase. Eur J Biochem. 1988;176:237-42 pubmed
    ..have been tested as potential substrates of partially purified rat hepatoma (HTC) cell or pure bovine spleen spermine synthase (EC 2.5.1.22)...
  52. Abela L, Simmons L, Steindl K, Schmitt B, Mastrangelo M, Joset P, et al. N(8)-acetylspermidine as a potential plasma biomarker for Snyder-Robinson syndrome identified by clinical metabolomics. J Inherit Metab Dis. 2016;39:131-7 pubmed publisher
    ..Clinical exome sequencing identified a novel missense mutation in the spermine synthase gene (SMS) that causes Snyder-Robinson syndrome (SRS)...
  53. Rogers R, Stevenson R, Simensen R, Holden K, Schwartz C. Finding new etiologies of mental retardation and hypotonia: X marks the spot. Dev Med Child Neurol. 2008;50:104-11 pubmed publisher
    ..This article provides an overview of MR and its association with hypotonia, with a review of five 'new' XLMR-hypotonia syndromes. ..