Report of a case of grey matter heterotopia combined with epilepsy due to TUBB2B gene variant and review of literature / 中华神经科杂志

Objective:To report the clinical phenotype and mutation site of a patient with grey matter heterotopia caused by a de novo heterozygous missense mutation in the TUBB2B gene, and to expand the phenotypic and mutational spectrum of TUBB2B mutations. Methods:One patient with TUBB2B mutation who presented to the Department of Neurology, the First Affiliated Hospital of Air Force Medical University in July 2017 was collected and analyzed for clinical features and mutation site, and a review of previous studies was performed. Results:The male patient started at the age of 18 and presented mainly with seizures, poor left-handed fine motor skills and poor spatial imagination. Magnetic resonance imaging showed nodular grey matter heterotopia in the right cerebral hemisphere, right frontoparietal-temporal localized cerebral gyrus, and cerebral sulcus shallow flat.The whole exon gene test suggested a heterozygous missense mutation in the TUBB2B gene: c.776 C>T (p.Pro259Leu), which was wild-type in both of his parents. The mutation site was located between the tubulin and tubulin-c structural domains and did not affect the function of the essential structural domain. After treatment with magnesium valproate in combination with levetiracetam, the patient′s seizure symptoms were significantly controlled and he has been seizure-free for 3 years now. Conclusions:The TUBB2B gene c.776 C>T (p.Pro259Leu) heterozygous missense mutation is a novel missense mutation causing grey matter heterotopia. The patient had a good prognosis, and the combination of two antiepileptic drugs resulted in complete seizure control.

Analysis of three patients with KBG syndrome and epileptic seizures due to variants of ANKRD11 gene / 中华医学遗传学杂志

OBJECTIVE@#To summarize the clinical phenotype and genotypic characteristics of 3 patients with KBG syndrome and epileptic seizure.@*METHODS@#Clinical data of the patients were collected. Family-trio whole exon sequencing (WES) was carried out. Candidate variants were verified by Sanger sequencing.@*RESULTS@#Patients 1 and 2 were boys, and patient 3 was an adult woman. All patients had epileptic seizures and mental deficiency. Their facial features included triangular face, low hair line, hypertelorism, large forward leaning auricles, broad nasal bridge, upturned nostrils, long philtrum, arched upper lip, and macrodontia. The two boys also had bilateral Simian creases. WES revealed that the three patients all harbored heterozygous de novo frameshift variants in exon 9 of the ANKRD11 gene including c.2948delG (p.Ser983Metfs*335), c.5397_c.5398insC (p.Glu1800Argfs*150) and c.1180_c.1184delAATAA (p.Asn394Hisfs*42). So far 291 patients with ANKRD11 gene variants or 16q24.3 microdeletions were reported, with over 75% being de novo mutations.@*CONCLUSION@#Above findings have enriched the spectrum of ANKRD11 gene mutations underlying KBG syndrome. WES is helpful for the early diagnosis of KBG, and provided reference for genetic counseling of this disease.

Analysis of reoperation rate and risk factors of adjacent segment disease after transforaminal lumbar interbody fusion / 中华骨科杂志

Objective:To explore the reoperation rate and risk factors of adjacent segment disease (ASDis) in patients with lumbar degenerative diseases after transforaminal lumbar interbody fusion (TLIF).Methods:The clinical data of 460 patients who underwent TLIF for lumbar degenerative diseases in our hospital from January 2011 to December 2013 were retrospectively analyzed. There were 204 males and 256 females with an age of 54.6±12.6 years (range, 20-85 years). Divided into ASDis group and None ASDis (N-ASDis) group according to the occurrence of ASDis and received surgical treatment. The age of ASDis group was 57.9±12.2 years, with 14 males and 12 females, while the age of N-ASDis group was 54.4±12.5 years, with 188 males and 246 females. Count the reoperation rate of ASDis. Compare the age, body mass index (BMI), comorbidities, surgery-related parameters, length of stay, imaging parameters before and after surgery between the two groups, and use univariate analysis and logistic regression analysis to explore risk factors for ASDis.Results:Among 460 patients who underwent TLIF due to lumbar degenerative diseases, 26 patients developed ASDis and received surgical treatment, the reoperation rate was about 5.7%. Among them, the reoperation rate of ASDis with above Pfirrmann grade III in the adjacent intervertebral disc was about 53.1% (17/32). The average onset time of adjacent segment disease was 76.3±25.0 months (range, 30-111 months). Univariate analysis showed that BMI ( t=3.86, P<0.001), history of hypertension (χ 2=5.30, P=0.021), preoperative adjacent vertebral disc degeneration (χ 2=85.90, P<0.001), preoperative adjacent spinal canal stenosis (χ 2=25.35, P<0.001), and preoperative intervertebral space height of adjacent segments ( t=4.33, P<0.001) were statistically different among patients with or without ASDis. Incorporating the above indicators into the logistic regression model, the analysis results showed that body mass index (BMI) >24.9 kg/m 2 and preoperative adjacent intervertebral disc degeneration ≥III degree were risk factors for ASDis after TLIF. Conclusion:The reoperation rate of ASDis after TLIF in patients with lumbar degenerative disease is about 5.7%. BMI>24.9 kg/m 2 and preoperative adjacent intervertebral disc degeneration ≥III degree are risk factors for ASDis and received surgical treatment after TLIF.

New variants in FLNA gene cause periventricular nodular heterotopia and epileptic seizure in three cases / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic bases of 3 patients with periventricular nodular heterotopia and epileptic seizure.@*METHODS@#The clinical data of three patients presenting with periventricular nodular ectopic with epileptic seizure were analyzed. Whole exome sequencing (WES) was performed on the patients, and Sanger sequencing was used to validate the suspected variants.@*RESULTS@#In three female patients, head MRI showed nodular gray matter ectopic in the bilateral ventricle. WES identified the heterozygous c.2720del T(p.Leu907Argfs*39) variant of FLNA gene in case 1 and her mother (case 2), and heterozygous c.1387_1390del GTGC(p.Val463Profs*34) of FLNA gene in case 3. According to the American College of Medical Genetics and Genomics standards and guidelines, the c.2720delT(p.Leu907Argfs*39) and c.1387_1390del GTGC (p.Val463Profs*34) variants of FLNA gene were predicted to be pathogenic (PVS1+PM2+PP1) and likely pathogenic(PVS1+PM2), respectively.@*CONCLUSION@#The c.2720delT(p.Leu907Argfs*39) and c.1387_1390del GTGC(p.Val463Profs*34) variants of FLNA gene may be the genetic cause of the three patients.

Correlation Study Between Serum Level of Soluble Semaphorin 4D and Ventricular Remodeling in Patients With Dilated Cardiomyopathy / 中国循环杂志

Objectives: To study the changes of blood levels of soluble semaphorin 4D (sSema4D) and matrix metalloproteinases-14 (MMP-14);to explore the correlation between sSema4D and ventricular remodeling in patients of dilated cardiomyopathy with chronic heart failure. Methods: Our research included in 2 groups:Dilated cardiomyopathy group, n=86 patients and Control group, n=32 healthy subjects. Blood levels of sSema4D, MMP14, Pro-BNP and hs-CRP were examined by ELISA. Left atrial diameter (LAD), right ventricular diameter (RVD), ejection fraction (EF), left ventricular end diastolic diameter (LVEDD), left ventricular fractional shortening (LVFS) were measured by echocardiography. Correlation analysis between blood levels of sSema4D, MMP-14 and the parameters for left ventricular remodeling was conducted. Results: Blood levels of sSema4D and MMP14 were different between 2 groups, P Conclusion: Serum level of sSema4D might be related to ventricular remodeling in patients with dilated cardiomyopathy which could be used as risk factor for predicting the prognosis of heart failure in relevant patients.

Effect of Phosphocreatine on Angiotensin II Induced Proliferation and Collagen Synthesis of Cardiac Fibroblasts in Neonatal Rats With its Mechanism / 中国循环杂志

Objective: To investigate the effect of phosphocreatine (PCr) on angiotensin II (Ang II) induced proliferation and collagen synthesis of cardiac ifbroblasts in neonatal rats with its mechanism. Methods: The cardiac ifbroblasts (CF) from neonatal rats were cultured in vitro and were divided into 4 groups.①Control group, the CF was cultured in non-serum DMEM,②Ang II group, the CF was cultured with Ang II at (1×10-6) mol/L,③PCr treated group, the CF was cultured with PCr at 10 mmol/L, and④Ang II+PCr group. The CF cell cycle percentage was detected by lfow cytometric assay, myocardial collagen content was observed by VG staining and protein expression of phosphorylated extracellular signal-regulated kinase (pERK1/2) was detected by immuneohistochemistry. Results: ① Compared with Control group, the CF in Ang II group showed increased percentage of S phase and decreased percentage of G0/G1 and G2/M phases, increased collagen content and pERK1/2 protein expression, all P0.05. ③ Compared with Control group, Ang II + PCr group had elevated pERK1/2 protein expression, P0.05.④Compared with Ang II group, the CF in Ang II + PCr group had increased percentage of G0/G1 and G2/M phases, decreased percentage of S phase, decreased collagen content and pERK1/2 protein expression, all P Conclusion: PCr may partially inhibit Ang II induced CF proliferation and collagen synthesis which might be related to the inhibition of excessively activated ERK1/2. Therefore, PCr could improve Ang II induced myocardial ifbrosis in neonatal rats.