Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a 3 years and 4 months old girl with autistic features, developmental delay, mental retardation, language impairment and dysmorphic features, carrying a 2.8 Mb de novo deletion of chromosome 2q24.2-->q24.3 detected by array-CGH. This region contains two neuronal voltage-gated sodium channel genes SCN2A and SCN3A.
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PMID:Array-CGH detection of a de novo 2.8 Mb deletion in 2q24.2-->q24.3 in a girl with autistic features and developmental delay. 2034 23

In this report, we describe a 15-year-old Malaysian male patient with a de novo SCN1A mutation who experienced prolonged febrile seizures after his first seizure at 6 months of age. This boy had generalized tonic clonic seizure (GTCS) which occurred with and without fever. Sequencing analysis of voltage-gated sodium channel a1-subunit gene, SCN1A, confirmed a homozygous A to G change at nucleotide 5197 (c.5197A > G) in exon 26 resulting in amino acid substitution of asparagines to aspartate at codon 1733 of sodium channel. The mutation identified in this patient is located in the pore-forming loop of SCN1A and this case report suggests missense mutation in pore-forming loop causes generalized epilepsy with febrile seizure plus (GEFS+) with clinically more severe neurologic phenotype including intellectual disabilities (mental retardation and autism features) and neuropsychiatric disease (anxiety disorder).
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PMID:Generalized epilepsy with febrile seizure plus (GEFS+) spectrum: Novel de novo mutation of SCN1A detected in a Malaysian patient. 2324 92

Neuromodulation mediated by metabotropic glutamate receptors (mGluRs) regulates many brain functions. However, the functions of mGluRs in the auditory system under normal and diseased states are not well understood. The medial nucleus of the trapezoid body (MNTB) is a critical nucleus in the auditory brainstem nuclei involved in sound localization. In addition to the classical calyx excitatory inputs, MNTB neurons also receive synaptic inhibition and it remains entirely unknown how this inhibition is regulated. Here, using whole-cell voltage clamp in brain slices, we investigated group I mGluR (mGluR I)-mediated modulation of the glycinergic and GABAergic inputs to MNTB neurons in both WT mice and a fragile X syndrome (FXS) mouse model (both sexes) in which the fragile X mental retardation gene 1 is knocked out (Fmr1 KO), causing exaggerated activity of mGluR I and behavioral phenotypes. Activation of mGluR I by (RS)-3,5-dihydroxyphenylglycine (3,5-DHPG) increased the frequency and amplitude of glycinergic spontaneous IPSCs (sIPSCs) in both WT and Fmr1 KO neurons in a voltage-gated sodium channel-dependent fashion, but did not modulate glycinergic evoked IPSCs (eIPSCs). In contrast, 3,5-DHPG did not affect GABAergic sIPSCs, but did suppress eIPSCs in WT neurons via endocannabinoid signaling. In the KO, the effect of 3,5-DHPG on GABAergic eIPSCs was highly variable, which supports the notion of impaired GABAergic signaling in the FXS model. The differential modulation of sIPSC and eIPSC and differential modulation of glycinergic and GABAergic transmission suggest distinct mechanisms responsible for spontaneous and evoked release of inhibitory transmitters and their modulation through the mGluR I signaling pathway.SIGNIFICANCE STATEMENT Neurons communicate with each other through the release of neurotransmitters, which assumes two basic modes, spontaneous and evoked release. These two release modes are believed to function using the same vesicle pool and machinery. Recent works have challenged this dogma, pointing to distinct vesicle release mechanisms underlying the two release modes. Here, we provide the first evidence in the central auditory system supporting this novel concept. We discovered neural-transmitter- and release-mode-specific neuromodulation of inhibitory transmission by metabotropic glutamate receptors and revealed part of the signaling pathways underlying this differential modulation. The results establish the foundation for a multitude of directions to study physiological significance of different release modes in auditory processing.
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PMID:Neurotransmitter- and Release-Mode-Specific Modulation of Inhibitory Transmission by Group I Metabotropic Glutamate Receptors in Central Auditory Neurons of the Mouse. 3009 38