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FB2026_02
,
released June 18, 2026
This report describes intellectual disability, X-linked, syndromic, Snyder-Robinson type; an alternative designation of this disease is 'mental retardation, X-linked, syndromic, Snyder-Robinson type' (MRXSSR). MRXSSR exhibits X-linked recessive inheritance. The human gene implicated in this disease is spermine synthase (SMS), which catalyzes the production of the polyamine spermine from spermidine; the correct spermine:spermidine ratio is critical for normal growth and development. There is a single orthologous gene in Drosophila, Dmel\Sms, for which RNAi targeting constructs and alleles caused by insertional mutagenesis have been generated.
Multiple UAS constructs of the human Hsap\SMS gene have been introduced into flies, including a tagged wild-type form and a construct carrying a variant implicated in Snyder-Robinson syndrome. Heterologous rescue (functional complementation) has been demonstrated: ubiquitous expression of the wild-type human gene rescues the reduced viability observed for a loss-of-function mutation of Dmel\Sms. A transgenic human gene with a pathological variant effects only partial rescue. Variant(s) implicated in human disease tested (as transgenic human gene, SMS): the Q148R variant form has been introduced into flies (designated Hsap\SMS443.UAS.Tag:FLAG in FlyBase).
Animals homozygous for a loss-of-function insertional mutation of Dmel\Sms exhibit semi-lethality, with only a small proportion of individuals reaching adulthood; surviving adults are short-lived and exhibit severe locomotor impairment in negative geotaxis assays. The eyes of homozygous adults exhibit several age-dependent defects, including abnormal vacuoles in the retina at day 2 after eclosion and neurophysiology defects. Several physical interactions for Dmel\Sms have been described; see below and in the Sms gene report.
[updated Feb. 2018 by FlyBase; FBrf0222196]
Intellectual disability is characterized by impairments in intellectual functioning and adaptive behavior; symptoms must be present before a child becomes 18 years old (http://medical-dictionary.thefreedictionary.com/mental+retardation; 2016.01.19).
Intellectual disability can be subdivided into syndromic forms, characterized by cognitive impairment accompanied by dysmorphic features, malformations or neurological abnormalities, and nonsyndromic forms, characterized by cognitive impairment without additional features (Basel-Vanagaite, 2008; DOI: 10.1002/9780470015902.a0021454).
[INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED, SYNDROMIC, SNYDER-ROBINSON TYPE; MRXSSR](https://omim.org/entry/309583)
[SPERMINE SYNTHASE; SMS](https://omim.org/entry/300105)
Developmental delay usually presents as failure to meet early developmental milestones and then evolves to moderate to profound global intellectual disability (which appears to remain stable over time) and variable motor disability. [from Gene Reviews, Snyder-Robinson Syndrome; 2018.02.26]
MRXSSR is an X-linked intellectual disability syndrome with characteristic features including facial asymmetry, marfanoid habitus, unsteady gait, thickened lower lip, nasal dysarthic speech, narrow or cleft palate, diminished muscle mass, osteoporosis, kyphoscoliosis, long great toes, short stature, pectus carinatum, and myopia (summary by Zhang et al., 2013; pubmed:23696453). [from MIM:309583; 2018.02.26]
Snyder-Robinson mental retardation syndrome (MRXSSR) is caused by mutation in the spermine synthase gene (SMS); X-linked recessive inheritance. [from MIM:309583; 2018.02.26]
The protein encoded by SMS catalyzes the production of spermine from spermidine. [Gene Cards, SMS; 2018.02.06]
The nearly ubiquitous polyamines (putrescine, spermidine and spermine) are polycationic mediators of cell proliferation and differentiation whose functions likely provide both stability and neutralization for nucleic acids (http://www.ebi.ac.uk/interpro/entry/IPR001045).
The correct spermine:spermidine ratio is critical for normal growth and development (Pegg, 2016; pubmed:27268251).
Spermine synthase is 1 of 4 enzymes involved in the synthesis of polyamines from arginine and methionine. [from MIM:300105; 2018.02.26]
One to one: 1 human to 1 Drosophila
High-scoring ortholog of human SMS (1 Drosophila to 1 human); Dmel\Sms shares 42% identity and 60% similarity with the human gene.