Mutations in ionotropic AMPA receptor 3 alter channel properties and are associated with moderate cognitive impairment in humans.

Ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (iGluRs) mediate the majority of excitatory synaptic transmission in the CNS and are essential for the induction and maintenance of long-term potentiation and long-term depression, two cellular models of learning and memory. We identified a genomic deletion (0.4 Mb) involving the entire GRIA3 (encoding iGluR3) by using an X-array comparative genomic hybridization (CGH) and four missense variants (G833R, M706T, R631S, and R450Q) in functional domains of iGluR3 by sequencing 400 males with X-linked mental retardation (XLMR).

[Clinical studies on fifty-seven Chinese patients with combined methylmalonic aciduria and homocysteinemia].

Objective: Methylmalonic aciduria (MMA) is a common one of the congenital disorders of organic acids metabolism. Some of the patients with the disorder are complicated with homocysteinemia. Recently, gas chromatography-mass spectrometry (GCMS) has been used to diagnose MMA in China.

Alpers syndrome with prominent white matter changes.

Alpers syndrome is a fatal neurogenetic disorder caused by the mutations in POLG1 gene encoding the mitochondrial DNA polymerase gamma (polgamma). Two missense variants, c.248T > C (p.

Spinal cord demyelination associated with biotinidase deficiency in 3 Chinese patients.

Biotinidase deficiency is a treatable cause of severe neurological disorders and skin problems. Spinal cord impairment is a rare complication of this disease and is commonly unrecognized. The authors encountered 3 Chinese patients with progressive spinal cord demyelination associated with biotinidase deficiency.

ARSA gene mutations in five Chinese metachromatic leukodystrophy patients.

The objective was to identify arylsulfatase A mutations, if any, in five Chinese patients with metachromatic leukodystrophy. This would be the first such study in China. All eight exons and exon-intron boundaries of the arylsulfatase A gene (ARSA) were amplified with polymerase chain reaction, which was followed by direct DNA sequencing.

[Clinical features and genotype-phenotype studies of 89 Chinese patients with X-linked adrenoleukodystrophy].

Objective: X-linked adrenoleukodystrophy (X-ALD) is the most common inherited disorder of peroxisomal metabolism which is characterized by demyelination of central nervous system, impaired adrenal cortex and abnormal accumulation of very long chain fatty acids in body fluid and tissues. In this study, the clinical features and the genotype-phenotype relationship were investigated so as to help early diagnosis.

Methods: Clinical data of 89 Chinese patients with X-ALD were analyzed and mutation spectrums in 53 of the patients were investigated by polymerase chain reaction and DNA sequencing.

[Clinical characteristics of cases with leukoencephalopathy with vanishing white matter].

Objective: To analyze and review the characteristics of leukoencephalopathy with vanishing white matter (VWM).

Methods: The clinical features including clinical manifestations, neurologic signs, cranial MRI and laboratory tests in 9 patients with the diagnosis of VWM were analyzed and the characteristics of the disease were reviewed.

Clinical Manifestations: 8 cases had symptoms involving central nervous system, 1 case only showed abnormal cranial MRI findings.

Alterations of NR2B and PSD-95 expression after early-life epileptiform discharges in developing neurons.

As an extreme form of abnormally synchronized activity, epilepsy may modify patterns of organization in the nervous system. It is clear that enhanced glutamatergic excitatory synaptic transmission with alterations in the expression of ionotropic glutamate receptors is a mechanism critical for seizure susceptibility and excitotoxicity. However, the exact quomodo and the roles of regulated N-methyl-D-aspartate receptor (NMDAR) composition and expression of a major postsynaptic density (PSD) scaffolding molecule, PSD-95, are as yet unclear.

[Diagnostic value of muscle, sural nerve and skin biopsies in childhood neuromuscular disorders].

Objective: To elicit the usefulness of muscle, sural nerve and skin biopsies in neuromuscular disease, including its diagnostic value and indications for biopsy.

Method: The authors retrospectively evaluated the clinical data of every patient who underwent muscle, sural nerve and/or skin biopsy in the department between January 1999 and December 2004.

Result: One hundred and two patients with the suspected neuromuscular diseases were included.

Clinical and biochemical studies on Chinese patients with methylmalonic aciduria.

Methylmalonic aciduria is a common organic aciduria disease. Recently, gas chromatography-mass spectrometry has been used to diagnose methylmalonic aciduria in China. Often, however, the diagnosis of methylmalonic aciduria is delayed because of a lack of technical expertise and the limited experience of general clinicians in China.

CACNA1I is not associated with childhood absence epilepsy in the Chinese Han population.

This study investigated whether the T-type calcium channel gene CACNA1I causes susceptibility in the Chinese Han population to childhood absence epilepsy, a form of idiopathic generalized seizure disorder. For this investigation, we searched for mutations in the 35 exons and exon-intron boundaries of the CACNA1I gene in 50 Han Chinese patients with childhood absence epilepsy. Seventeen single nucleotide polymorphisms were identified in the 35 exons.

New variants in the CACNA1H gene identified in childhood absence epilepsy.

Childhood absence epilepsy (CAE) is a common form of idiopathic generalized epilepsy with polygenic inheritance. In our previous studies, relatively high frequent variants in the T-type calcium channel gene, CACNA1H, were identified in the Chinese Han population, most of which are located in exons 6-12. The goal of this study was to identify additional variants in this region of the CACNA1H gene.

[Analysis of ARSA mutations in a Chinese family with metachromatic leukodystrophy].

Objective: To identify arylsulftase A gene (ARSA) mutations in a Chinese family with MLD.

Methods: There were two MLD patients in the investigated family. The proband, an 11-year-old girl, was well until the age of 5 years, when she began to experience difficult walking and mental regression.

[The effect of CACNA1H gene G773D mutation on calcium channel function].

Objective: To study the effect of CACNA1H gene mutation G773D on calcium channel function.

Methods: By the overlap extension PCR we introduced G773D mutation into a human Cav3.2acDNA for constructing the mutant.

Acute metabolic crisis induced by vaccination in seven Chinese patients.

Seven Chinese patients (5 males and 2 females) with vaccination-induced acute metabolic crisis were reported. Only one male with 21-hydroxylase deficiency had been diagnosed before vaccination. In the remaining six patients, the preexisting diagnoses were not confirmed before the vaccination.

[Clinical characteristics and long-term prognosis of Landau-Kleffner syndrome].

Objective: To investigate the clinical and electroencephalographic (EEG) characteristics, therapeutic response and long-term prognosis of Landau Kleffner syndrome (LKS).

Methods: The clinical and EEG data of 10 children with LKS were analyzed, and therapeutic response and long-term outcome were followed up.

Results: The age of onset was from 2 to 10.

Clinical and laboratory survey of 65 Chinese patients with Leigh syndrome.

Background: Leigh syndrome is an inherited neurodegenerative disease that emerges in infancy and childhood and presents with a clinically heterogeneous variety of neuromuscular and non-neuromuscular disorders. It can result from the inheritance of mutations in either nuclear or mitochondrial DNA. In the current study, we performed a retrospective study in 65 patients in order to investigate the clinical and genetic characteristics of Leigh syndrome in Chinese patients.

Long-term effect of early discharge on sEPSC and [Ca2+]i in developing neurons.

To study the long-term changes induced in immature rat cortical neuronal cultures by transient exposure to an Mg(2+)-free treatment, at cultured day 6, cells were assigned into three groups, based on the mediums they were transiently exposed to as follows: control group 1 (CONT1) was exposed to Dulbecco's Modified Eagle's Medium (DMEM), control group 2 was exposed to a physiological solution (PS), and the magnesium-free physiological solution group (MGFPS) was exposed to the same medium as CONT2 except for the removal of magnesium. Following a 3-h exposure, the amplitude and frequency of spontaneous excitatory postsynaptic currents (sEPSC) were recorded and intracellular calcium concentrations ([Ca2+]i) were measured. Compared to the CONT1 and CONT2 groups, the MGFPS group displayed a significantly greater amplitude (at d6, d7, d9, and d12) and frequency (at d6, d7, and d9) of sEPSC (p<0.

The genotype and phenotype studies of 40 Chinese patients with X-linked adrenoleukodystrophy (X-ALD).

Objective: To elucidate the phenotype and the genotype-phenotype correlations in Chinese patients with X-linked adrenoleukodystrophy (X-ALD).

Methods: Clinical features of 40 Chinese patients with X-ALD were studied and mutation spectrums were investigated by polymerase chain reaction (PCR) and sequencing.

Results: Among these patients, four were siblings from two unrelated families, the others were unrelated.

ABCD1 gene mutations in Chinese patients with X-linked adrenoleukodystrophy.

X-linked adrenoleukodystrophy is a neurodegenerative disorder caused by mutations in the adrenoleukodystrophy (ALD) protein gene ABCD1. This study used direct sequencing of genomic polymerase chain reaction products to perform mutational analysis of ABCD1 in 34 unrelated Chinese X-linked adrenoleukodystrophy patients and 27 of their maternal relatives. Thirty-two different mutations were identified in 34 patients.

c-Fos, N-methyl-d-aspartate receptor 2C, GABA-A-alpha1 immonoreactivity, seizure latency and neuronal injury following single or recurrent neonatal seizures in hippocampus of Wistar rat.

To evaluate the long-term effects of single or recurrent prolonged neonatal seizures on seizure threshold and neuronal activity in the brain, a novel "twist" seizure was induced by coupling early-life flurothyl-induced seizures with later exposure to pentylenetetrazol. The authors assigned six neonatal rats for each group: the single-seizure group (SS), the recurrent-seizure group (RS) and the control group. At postnatal day 46, seizure threshold was examined using pentylenetetrazol, and then the brain slices were evaluated with thionine staining, in situ end labeling and immunohistochemical studies.

Case-control study and transmission/disequilibrium tests of the genes encoding GABRA5 and GABRB3 in a Chinese population affected by childhood absence epilepsy.

Background: Childhood absence epilepsy (CAE) is one of the most frequently recognized syndromes among the idiopathic generalized epilepsies (IGEs). CAE is considered to be a genetic disease, with a possible polygenic inheritance pattern. The genes responsible for CAE have not been identified yet.