Analysis of the clinical presentation and genetic profile of epilepsy-aphasia spectrum due to GRIN2A gene mutations / 中华神经科杂志

Objective:To explore the clinical phenotypic features and genetic variation characteristics of children with epilepsy-aphasia spectrum due to GRIN2A gene variants confirmed by second-generation sequencing. Methods:The clinical data of 5 children with epilepsy-aphasia spectrum with epileptic onset diagnosed in the Department of Neurology, Children′s Hospital Affiliated to Zhengzhou University, from February 2019 to November 2022 were retrospectively analyzed. Whole-exome genome sequencing of the probands using a second-generation sequencing method confirmed that all 5 cases were children with the GRIN2A gene variant. The characteristics of the GRIN2A gene variants were analyzed. Results:Among the 5 children diagnosed with epileptic aphasia spectrum due to GRIN2A gene variants, the male-to-female ratio was 4∶1, and the age range of onset was 1.5-4.4 years. The clinical phenotype included seizures in all cases, language and intellectual developmental deficits in 4 cases, and attention deficit hyperactivity disorder in 3 cases. The seizures were manifested as focal seizures or secondary generalized seizures, and were effectively controlled with antiepileptic drugs. Among the 5 children, gene variant of case 1 was originated from a paternal heterozygous variant, and cases 2-5 had de novo variants, which were c.2107C>T (p.Gln703 *) nonsense variant, c.2284G>A (p.Gly762Arg) missense variant, c.2197del (p.Ala733Glnfs *3) shifted coding variant, c.2511G>A (p.Trp837 *) nonsense variant, and c.1651+1G>C shear site variant, respectively. None of the 5 loci were reported in the literature. Conclusions:Epilepsy-aphasia spectrum is an epilepsy syndrome with a complex onset, and may have different phenotypes at different genetic variant loci, with focal seizures or secondary generalized seizures, which can be effectively controlled with anti-seizure medication. The GRIN2A gene variant is the genetic etiology of the epileptic aphasia spectrum.

Clinical characteristics and genetic analysis of childhood onset neurodegeneration associated with UBTF gene variation / 中华神经科杂志

Objective:To summarize the clinical phenotype and genetic characteristics of children with neurodegeneration caused by UBTF gene mutations in childhood. Methods:The clinical and genetic data of 3 children with neurodegeneration in childhood diagnosed in the Department of Neurology, Children′s Hospital Affiliated to Zhengzhou University from February 2020 to January 2023 were retrospectively analyzed. All the 3 probands were found having UBTF gene mutations through the whole exome gene sequencing, and the first generation Sanger sequencing method was used to verify the UBTF gene in their family members. The variation characteristics of the UBTF gene were analyzed, and the treatment and follow-up results of the 3 children were summarized. Results:Among the 3 children with childhood onset neurodegeneration, 2 were male and 1 female, aged 9 months, 4 years and 6 months after birth, respectively. The clinical phenotypes mainly included motor retardation, speech and mental retardation, and dystonia. Among them, case 1 and case 2 had seizures, case 1 had dysphagia, feeding problems, no weight gain and ataxia. Brain MRI plain scan showed that case 1 and case 2 had different degrees of cerebral atrophy, case 1 had hypoplasia of corpus callosum, ventricle expansion and softening focus, and case 3 showed non-specific widening of the subarachnoid space. There were no abnormalities in the chromosome copy number variation and mitochondrial ring gene testing in the 3 children; the whole exon gene testing suggested the de novo missense variant in the UBTF gene [NM_014233.4: c.1414(exon14) G>A (p.Gly472Ser), c.1392(exon14)G>T(p.Lys464Asn)] and the maternal nonsense variant [NM_014233.4:c.520C>T(p.Arg174 *)], which were unreported site variants. In terms of treatment, the 3 children received comprehensive rehabilitation function training, and achieved a certain degree of language and intelligence improvement. Seizure control was effectively managed in case 1 with a single antiepileptic drug. Epileptic seizures were effectively treated and controlled in case 2 using more than 4 types of antiepileptic drugs. Conclusions:Neurodegenerative changes caused by UBTF gene mutations in childhood are relatively rare, and some cases may be accompanied with brain atrophy. De novo missense variation and maternal nonsense variation of the UBTF gene are the genetic etiology of the 3 probands.

A case of glutathione synthetase deficiency due to compound heterozygous variant of glutathione synthase gene / 中华神经科杂志

The clinical data and gene variant characteristics of a patient with glutathione synthetase (GSS) deficiency were summarized. The child was born 15 min prematurely as a male infant with postnatal respiratory distress, metabolic acidosis, severe anemia, hemolysis, hyperbilirubinemia, and motor developmental backwardness. Blood and urine genetic metabolic screening showed a blood glutamate value of 1 343.1 μmol/L and a urine 5-oxoproline value of 1 873.7 nmol/mg creatinine. Cranial magnetic resonance imaging showed nonspecific subarachnoid widening. Whole-exon gene sequencing of the family line suggested that the GSS gene of the preexisting patient originated from paternal and maternal variants, respectively: c.632_633del (p.Gln211Argfs *8), and c.491G>A (p.Arg164Gln). Complex heterozygous variants of the GSS gene were the genetic etiology of the present case.

Progress of serum cystatin C in patients with type 2 diabetes mellitus and the complications / 中国综合临床

Objective Cystatin C (CysC) is a cysteine protease inhibitor,is widely expressed in human eukaryotic cells,CysC involved in diabetic nephropathy,retinopathy,peripheral vascular disease and type 2 diabetes,insulin resistance occurs Development,as a predictor of type 2 diabetes and complications

The protective effect of fenofibrate on acute focal cerebral ischemia reperfusion injury in mice / 中国药学杂志

OBJECTIVE: To investigate the protective effect of fenofibrate (Fen) on acute focal cerebral ischemia reperfusion injury in mice and its mechanisms. METHODS: Cerebral ischemia was induced by middle cerebral artery occlusion in mice for 90min and then reperfusion. Fen (10, 80 mg · kg-1) was intragastrically administered at the same time of reperfusion and 2 h after reperfusion respectively. The neurological deficit score, infarct volume and brain edema degree were determined 24 h after reperfusion. At the same time the expression of PPARα mRNA in brain tissue was measured by real-time RT-PCR. The contents of maiondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in the brain tissue were measured by biochemical assay. The disruption of blood-brain barrier(BBB) was evaluated by the extravasations of Evans Blue (EB). MK886, an antagonist of PPARα receptor, was used to investigate the involvement of PPARα in the protective effect of Fen. RESULETS: Fen (80 mg · kg-1) ameliorated neurological function, reduced infarct volume, attenuated brain edema degree, decreased the extravasations of EB, increased the expression of PPARα mRNA, and attenuated the lipid peroxidation in brain tissues. MK886 abolished the protective effect of Fen. CONCLUSION: Fen has protective effect against acute focal cerebral ischemia reperfusion injury in mice by increasing the expression of PPARα mRNA and reducing lipid peroxidation in brain tissue.

Tissue distribution of s-oleylpropanolamide in rats detected by liquid chromatography with tandem mass spectrometry / 药学学报

This paper is to report the development of a rapid and sensitive method for the determination of s-oleylpropanolamide (OPA) in various tissues of rat (brain, heart, lung, liver, spleen, small intestine, kidney, adipose tissue and muscle), and to assess the applicability of the assay to tissue distribution. OPA was extracted by liquid-liquid extraction method with undecylenoylethanolamide as an internal standard. The concentrations of OPA were determined by LC-MS/MS after a single intragastric dose of 50 mg x kg(-1) at 4 time points (5 rats per group). With multiple reactions monitoring mode (MRM) the limit of quantification (LLOQ) was determined at 1 microg x L(-1). The calibration curve was linear from 1 to 2 x 104 microg x L(-1) (r > or = 0.999 0) for tissue homogenates. Validation parameters such as accuracy, precision and recovery were found to be within the acceptance criteria of the assay validation guidelines. The highest concentration was found in small intestine (the highest time point is 15 min) and heart (the highest time point is 90 min). The assay is rapid, sensitive and applicable to studying tissue distribution of OPA in rats.

Tissue distribution of s-oleylpropanolamide in rats detected by liquid chromatography with tandem mass spectrometry / 药学学报

This paper is to report the development of a rapid and sensitive method for the determination of s-oleylpropanolamide (OPA) in various tissues of rat (brain, heart, lung, liver, spleen, small intestine, kidney, adipose tissue and muscle), and to assess the applicability of the assay to tissue distribution. OPA was extracted by liquid-liquid extraction method with undecylenoylethanolamide as an internal standard. The concentrations of OPA were determined by LC-MS/MS after a single intragastric dose of 50 mg x kg(-1) at 4 time points (5 rats per group). With multiple reactions monitoring mode (MRM) the limit of quantification (LLOQ) was determined at 1 microg x L(-1). The calibration curve was linear from 1 to 2 x 104 microg x L(-1) (r > or = 0.999 0) for tissue homogenates. Validation parameters such as accuracy, precision and recovery were found to be within the acceptance criteria of the assay validation guidelines. The highest concentration was found in small intestine (the highest time point is 15 min) and heart (the highest time point is 90 min). The assay is rapid, sensitive and applicable to studying tissue distribution of OPA in rats.