ABSTRACT
Objective:To summarize the clinical features and gene mutation characteristics of a child with mitochondrial enoyl-CoA hydratase short chain 1 deficiency (ECHS1D) caused by enoyl-CoA hydratase short chain 1 ( ECHS1) gene mutation. Methods:The clinical characteristics and genetic test results of a child with ECHS1D who visited the Department of Neurology of Xuzhou Children′s Hospital in January 2021 were retrospectively analyzed, and the clinical features of the disease were also reviewed by searching relevant domestic and foreign literature.Results:The child was a 6 months and 4 days old male, with acute onset, the main clinical manifestation being limb movement disorder after admission. The child had slow motor development, his head was still upright and cannot turn over, the child also cannot sit alone, follow up and make a laugh, and the muscle tension of limbs was increased. The child′s blood lactate was increased to 6.2 mmol/L, which suggested metabolic acidosis, and magnetic resonance imaging (MRI) of the head showed abnormal signals in the basal ganglia on both sides, abnormal enhancement of the meninges of the left cerebral hemisphere. Whole exome sequencing revealed that the child had compound heterozygous mutations in ECHS1 gene, c.563C>T (p.A188V) and c.5C>T (p.A2V), respectively. The child′s father carried c.563C>T mutation, the mother carried c.5C>T mutation, all of which were missense mutations. Conclusions:ECHS1 gene mainly has missense mutations, most of which are compound heterozygous mutations, and a few are homozygous mutations. The ECHS1D caused by ECHS1 gene mutation often affects infants and young children. MRI suggests abnormal signals in the basal ganglia; for cases with the above clinical manifestations and abnormal signals in the basal ganglia on MRI, genetic testing should be considered to confirm the diagnosis.
ABSTRACT
Leigh syndrome (French-Canadian type, LSFC) is a rare autosomal recessive hereditary severe neurological disorder that begins in infancy. Herein we report a case with LSFC in China. The patient was 8 months old, male, whose clinical manifestations included delayed development, low muscle tone, unstable vertical head, inability to sit alone, cognitive impairment, slightly smaller forehead, oblique eyes, epilepsy, etc. Gene sequencing results showed that the LRPPRC gene in the infant had complex heterozygous mutations of c.2989G>A (newly reported) and c.4078G>A. Combined with the clinical manifestations, gene mutations and literatures, the infant was diagnosed as LSFC, and symptomatic rehabilitation was performed. The results of genetic testing can contribute to the early diagnosis and genetic counseling of LSFC patients, and help reduce the burden on the patients and their families.
ABSTRACT
Tuberous sclerosis complex (TSC) is an autosomal dominant hereditary cutaneous neurological syndrome.The clinical manifestations of TSC are complex and diverse,and many of them are skin lesions,brain nodules,cardiac rhabdomyoma,pulmonary vascular lymphoma,renal vascular leiomyoma and other body multiple hamartoma lesions and neuropsychiatric symptoms.The current studis have found that TSC1 and TSC2 are their causative genes.The pathogenesis of TSC and the latest research are summarized.
ABSTRACT
Objective To explore the changes of multidrug resistant-associated protein (MRP) 1 expression and MRP2 expression in the peripheral blood mononuclear cells in intractable epileptic children after accepting the Levetiracetam (LEV) add-on therapy.Methods From June 2012 to September 2015,68 intractable epileptic children who had been diagnosed at the Outpatient Department of the Xuzhou Children's Hospital were randomly selected and given the LEV add-on therapy.The expressions of MRP1 and MRP2 in their peripheral blood mononuclear cells were detected by real-time fluorescence quantitative polymerase chain reaction and Western blot before the LEV add-on therapy and 6 months after the LEV add-on therapy.Results (1) Compared to the expressions of MRP1 mRNA and MRP2 mRNA in the peripheral blood mononuclear of intractable epileptic children before therapy,the expressions of MRP1 mRNA (0.23 ± 0.02) and MRP2 mRNA (0.17 ±0.03) after therapy were obviously down-regulated with significant differences(tMRP1 =32.77,P ＜ 0.01;tMRP2 =26.73,P ＜ 0.01).(2) The relative expressions of protein of MRP1 and MRP2 in the peripheral blood mononuclear of intractable epileptic children before therapy were 0.59 ± 0.03,0.53 ± 0.02 respectively,and they were 0.39 ± 0.03,0.38 ± 0.02 after therapy.Compared with those before therapy,the protein expressions of MRP1 and MRP2 were down-regulated,and the differences were significant (tMRP1 =11.55,P＜0.01;tMRP2 =9.87,P＜0.01).Conclusions The expressions of MRP1 and MRP2 mRNA and protein in the peripheral blood mononuclear cells in some intractable epileptic children can be down-regulated if patients receive the LEV add-on therapy,and LEV may control the seizures of intractable epileptic children by down-regulating the expressions of MRP1 and MRP2,then reduce the occurrence and development of drug-resistant epilepsy.
ABSTRACT
Objective To study the expression of multidrug resistance associated protein 1 (MRP1) and MRP2 in the peripheral blood mononuclear cells of children with intractable epilepsy (IE).Methods During Nov.2010 to Oct.2013,50 children with I E were collected as the experimental group,simultaneously 50 children with epilepsy controlled by the anti-epileptic drugs (AEDs) and 50 healthy children without epilepsy were collected as the control group from the outpatient or inpatient of Xuzhou Children's Hospital.The expressions of MRP1 and MRP2 in the peripheral blood mononuclear cells of children were detected by reverse transcriptase polymerase chain reaction and Western blot.Results 1.The mean relative expression of MRP1 and MRP2 mRNA in the peripheral blood mononuclear cells of children with IE (0.795 ± 0.042,0.804 ± 0.023) were higher than those in epilepsy controlled by AEDs (0.682 ± 0.030,0.675 ± 0.021) and healthy children without epilepsy (0.665 ± 0.031,0.654 ± 0.029) (all P ＜0.001).2.The mean relative expression of MRP1 and MRP2 protein in the peripheral blood mononuclear cells of children with IE (2.027 ±0.034,1.902 ±0.021) were higher than those in epilepsy controlled by AEDs(1.131 ±0.042,1.086 ± 0.027) and healthy children without epilepsy (1.093 ± 0.023,1.045 ± 0.018) (all P ＜ 0.001).3.There was no difference in the expression of MRP1,MRP2 mRNA and proteins between the children with epilepsy controlled by AEDs and healthy children without epilepsy (all P ＞ 0.05).Conclusions MRP1 and MRP2 over-expression in the peripheral blood mononuclear cells of children with IE may be associated with drug-resistance mechanism for medically intractable epilepsy.
ABSTRACT
Objective To investigate the effects of amplitude dependent morphological and proliferative changes in human bladder smooth muscle cells (hBSMCs) undergoing physiological stretch in vitro.Methods The hBSMCs were cuhured on silicone membrane and stretched similarly to a bladder cycle at range of stretches and time.The elongation would increase up to 2.5％ every 3 h and 5％ (or 10％,15％,20％ and 25％ depending on the experiment design) in the next 1 h,followed by a rapid decrease,cyclically maintained for a total of 16 h.In subsequent 8 h (24 h cycles) the membrane was maintained in relaxed position.Immunofluorescence and confocal laser scanning microscope were employed to assess the morphological changes.Cell counting kit-8 (CCK-8) and flow cytometry were used to assess the cell proliferation.Results The hBSMCs showed contractile phenotype after application of mechanical strain.Compared with control,the strains at 5％,10％,15％,20％ and 25％ induced most of the cells to change from a more spread-out and stellate state with large cell surface contact areas to a typical spindle-like morphology.The orientation angle of BSMCs remarkably differed depending on the applied strain's magnitude.Absorbance value,which reflects the proliferation activity,analyzed by CCK-8 was improved from 0.471 ± 0.027 (control) to 1.320 ± 0.094 (5％ elongation group,P ＜ 0.0001),1.001 ± 0.029 (10％ elongation group,P ＜0.0001),0.821 ±0.032 (15％ elongation group,P＜0.0001),0.621 ±0.032 (20％ elongation group,P =0.0004) and 0.591 ± 0.056 (25％ elongation group,P =0.0268),respectively.Cell proliferation index increased from (29.35 ±0.55)％ (control) to (55.55 ± 1.05)％ (5％ elongation group,P ＜0.0001),(47.70 ±0.20)％ (10％ elongation group,P＜0.0001),(35.40 ±2.10)％ (15％ elongation group,P ＜0.0001),respectively.However,no significant difference was found in either 20％ elongation group (34.85 ±0.55)％ (P=0.1372) or 25％ elongation group (30.35 ±0.45)％ (P=0.5234).Conclusions Proliferative and morphological changes could be observed in hBSMCs in vitro.Maximal proliferative potential could be seen at 5％ of stretch.
ABSTRACT
The mechanism of drug resistance of refractory epilepsy has remained unclear.In recent years,studies have shown that the multi-drug resistance associated protein(MRP) is related with refractory epilepsy.The mechanism responsible for the drug resistance may have something to do with the higher expression of MRP1 mRNA in brain tissues of refractory epilepsy patients.Through the use of drugs in cells to cells from the pump,it can reduce the drug concentration in brain and make the creation bears the medicine and inhibitors specific for MRP,which can significantly improve the effect of some antiepileptic drugs.Thus,further studies may provide new ways for the treatment of refractory epilepsy and find targets for new antiepileptic drugs.