X-linked spermine synthase gene (SMS) defect: the first polyamine deficiency syndrome.
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Cason AL, Ikeguchi Y, Skinner C, Wood TC, Holden KR, Lubs HA, Martinez F, Simensen RJ, Stevenson RE, Pegg AE, Schwartz CE
X-linked spermine synthase gene (SMS) defect: the first polyamine deficiency syndrome.
Eur J Hum Genet. 2003 Dec;11(12):937-44.
- PubMed ID
- 14508504 [ View in PubMed]
- Abstract
Polyamines (putrescine, spermidine, spermine) are ubiquitous, simple molecules that interact with a variety of other molecules in the cell, including nucleic acids, phospholipids and proteins. Various studies indicate that polyamines are essential for normal cell growth and differentiation. Furthermore, these molecules, especially spermine, have been shown to modulate ion channel activities of certain cells. Nonetheless, little is known about the specific cellular functions of these compounds, and extensive laboratory investigations have failed to identify a heritable condition in humans in which polyamine synthesis is perturbed. We report the first polyamine deficiency syndrome caused by a defect in spermine synthase (SMS). The defect results from a splice mutation, and is associated with the Snyder-Robinson syndrome (SRS, OMIM_309583), an X-linked mental retardation disorder. The affected males have mild-to-moderate mental retardation (MR), hypotonia, cerebellar circuitry dysfunction, facial asymmetry, thin habitus, osteoporosis, kyphoscoliosis, decreased activity of SMS, correspondingly low levels of intracellular spermine in lymphocytes and fibroblasts, and elevated spermidine/spermine ratios. The clinical features observed in SRS are consistent with cerebellar dysfunction and a defective functioning of red nucleus neurons, which, at least in rats, contain high levels of spermine. Additionally, the presence of MR reflects a role for spermine in cognitive function, possibly by spermine's ability to function as an 'intrinsic gateway' molecule for inward rectifier K(+) channels.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Spermine Spermine synthase Protein Humans YesLigandDetails - Polypeptides
Name UniProt ID Spermine synthase P52788 Details