Gene Mutation Characteristics Research Articles

Whole genome sequencing of colorectal neuroendocrine tumors and in-depth mutational analyses.

Colorectal neuroendocrine tumors (NETs) are rare neoplasms and studies on colorectal NETs are relatively few compared to other tumors. To better understand the pathogenesis of this tumor, we performed whole-genome sequencing and follow-up verification using Sanger sequencing of the colorectal NETs and paired para-tumor tissue. We analyzed the features of the gene mutation spectrum and mutation signature patterns, and analyzed the four pathways that were altered by gene mutation in pancreatic neuroendocrine tumors, including DNA damage and repair, chromatin remodeling, telomere maintenance and mTOR signaling activation. We found that PARP4 which is related to the DNA damage and repair pathway; TSC2, which is related to the mTOR signaling activation pathway; and SLX1A, which is related to telomere maintenance, were mutated in colorectal NETs. Our data analyzed characteristics of gene mutation in colorectal NETs at the whole-genome level, and may help to better understand the pathogenesis of colorectal NETs and may be helpful for potential tumor therapy in the future.

Clinical analysis of gene mutation characteristics and mutation burden in myelodysplastic syndrome

Objective: To investigate the relationship between gene mutation characteristics, mutation burden and general condition, disease subtype and karyotype of patients with myelodysplastic syndrome (MDS), and its clinical value. Methods: High-throughput sequencing was used to detect 65 blood tumor-related genes in 191 MDS patients and 9 secondary acute myelocytic leukemia patitents(SAML), and to analyze the characteristics of abnormal genes, mutation burden, as well as the relationship with disease subtypes, chromosome karyotypes and age. Results: Mutations were found in 148 patients (77.5%), including 47 abnormal genes and 186 mutation sites. And gene mutations were found in 9 SAML patients, the number of mutations was significantly higher than that in MDS patients (χ(2)=11.911, P=0.018). Among the abnormal genes, the mutation frequency of U2AF1 (37.3%) and ASXL1 (41.6%) were higher, and there were significant differences in mutation burden among different abnormal genes (F=91.946, P<0.001). There were differences in the number of gene mutations among different subtypes of MDS, and the number of EB-2 gene mutations was the highest (2.2±1.5). In SLD, MLD, EB-1 and EB-2, the proportion of carrying ≥ 3 mutations increased gradually (χ(2)=52.471, P=0.037). TP53 mutation was associated with abnormal karyotype (r(φ)=0.177, P=0.019), especially with complex karyotype (r(φ)=0.440, P<0.001), while NPM1 mutation is associated with normal karyotype (r(φ)=0.173, P=0.024). The number of mutations carried by patients under 30 years old was the least, and the number of mutations increased with the increase of age. The number of mutations was the most in patients aged 60 to 79 years old (P=0.017), and the mutation frequency of epigenetic related genes increased with the increase of age (P=0.041). Conclusions: The mutation characteristics and mutation load of MDS-related genes are closely related to clinical factors such as disease subtype, chromosome karyotype and patient age.

Characteristics of the isocitrate dehydrogenase gene and telomerase reverse transcriptase promoter mutations in gliomas in Chinese patients.

ObjectivesTo explore the characteristics of IDH and TERT promoter mutations in gliomas in Chinese patients.MethodsA total of 124 Chinese patients with gliomas were enrolled to study the frequencies of mutations in isocitrate dehydrogenase (IDH) and telomerase reverse transcriptase promoter (TERTp). Among the 124 patients, 59 patients were enrolled to study the classification of gliomas based on mutations in IDH and TERTp.ResultsIsocitrate dehydrogenase mutations are positively correlated with a good prognosis but mutations in TERTp cannot predict prognoses independently. The combined analysis of the mutations of IDH and TERTp can predict the prognosis more accurately. Patients with IDH and TERTp glioma mutations have the best prognosis, followed by only IDH mutation patients and only TERTp mutation patients, which have the worst prognosis. IDH and TERTp mutations occur frequently in males, younger patients or lower‐grade patients. In contrast, only TERTp mutations occur frequently in females, older patients or higher‐grade patients.ConclusionsPatients with IDH and TERTp glioma mutations have the best prognosis, and only IDH mutation patients and only TERTp mutation patients have the worst prognosis. Moreover, the molecular classification of gliomas by mutations of IDH and TERTp is not suitable for pediatric patients.

Clinical and Genetic Heterogeneity in a Cohort of Chinese Children With Dopa-Responsive Dystonia.

Background: The aim of this study was to investigate the genetic and clinical features of dopa-responsive dystonia (DRD) in China.Method: Characteristics of gene mutations and clinical manifestations of 31 patients diagnosed with DRD were analyzed retrospectively.Result: From January 2000 to January 2019, 31 patients were diagnosed with DRD. Twenty (64.5%) were male, and 11 (35.5%) were female. Ten patients (32.3%) had classic DRD, 19 (61.3%) had DRD-plus, and 2 (6.4%) patients had mutations in the dopamine synthetic pathway (PTS gene mutation) without a typical phenotype (not DRD or DRD-plus). Twenty-eight (90.3%) patients underwent genetic testing. Homozygous or compound heterozygous TH gene mutations were found in 22 patients. GCH1 and PTS gene mutations were found in 2 patients. Heterozygous TH mutation and genetic testing were negative in 1 patient. They took different doses of L-dopa, ranging from 0.4 to 8.7 mg/kg/d. Patients with classic DRD responded well. In patients with DRD-plus, 94.7% (18/19) responded well with residual symptoms. One patient (5.3%) did not show any improvement.Conclusion: DRD can be divided into classic DRD and DRD-plus. In this cohort, the most common pathogenic gene was TH. Fever was the important inducing factor of the disease. L-dopa has sustained and stable effects on patients with classic DRD. In patients with DRD-plus, treatment with L-dopa could ameliorate most of the symptoms.

新发MBTPS2基因突变致毛囊性鱼鳞病、秃发、畏光综合征一例

A case of ichthyosis follicularis, alopecia and photophobia syndrome caused by a novel mutation c.1165C>T in the membrane-bound transcription factor protease site 2 (MBTPS2) gene was firstly reported. The proband presented with dry skin, congenital hairlessness, follicular keratotic papules, photophobia, epilepsy, and mental and motor retardation. Next-generation and Sanger sequencing analysis confirmed that the proband and his mother both had a c.1165C>T (p.pro389Ser) mutation in exon 9 of the MBTPS2 gene. According to the clinical manifestations of the patient and genetic characteristics of the MBTPS2 gene mutation, the patient was diagnosed with ichthyosis follicularis, alopecia and photophobia syndrome. Key words: Ichthyosis; Alopecia; Photophobia; Point mutation; Ichthyosis follicularis, atrichia and photophobia syndrome

Characteristics of gene mutations in Chinese single-center pulmonary adenocarcinoma patients and comparison with European and American pulmonary adenocarcinoma populations

Objective To explore the characteristics and significances of gene mutations in pulmonary adenocarcinoma, and to provide evidence for targeted medication. Methods High throughput sequencing based target-capture sequencing was performed in 104 patients with pulmonary adenocarcinoma to detect the mutational status of 56 cancer-related genes. All patients were diagnosed in the First People's Hospital of Kunshan from May 2017 to August 2018. The mutational characteristics of pulmonary adenocarcinoma was analyzed and compared with European and American pulmonary adenocarcinoma populations. The correlations between mutational characteristics and clinical features were analyzed, and the mutation sites for targeted medication were screened. Results Among 104 patients with pulmonary adenocarcinoma, totally 34 mutational genes were detected in 84 patients (81%, 84/104). Highly frequent mutations included epidermal growth factor receptor (EGFR) (49%, 51/104), TP53 (21%, 22/104), KRAS (13%, 14/104), and BRAF (6%, 6/104). Among all the 187 variants, 76% (142/187) were non-synonymous missense mutations, 13% (24/187) were small fragment deletions, 6% (12/187) were copy number variants, 3% (5/187) were small fragment insertions, and 2% (4/187) were nonsense site mutations. Among 104 patients with pulmonary adenocarcinoma, 34 targeted drug-associated mutations of 13 genes were detected in 68 patients (65%), and 19 (18%) patients harbored ≥ 2 targeted drug-associated mutations. EGFR mutations were more common in female patients than in male patients [62% (34/55)vs. 35% (17/49), χ2= 7.629, P= 0.006], while KRAS mutations were more frequent in male patients than in female patients [22% (11/49) vs. 5% (3/55), χ2= 6.424, P= 0.011]. The mutation frequencies of gene EGFR, TP53, KRAS, and CDKN2A in Chinese single-center (the First People's Hospital of Kunshan) and European and American adenocarcinoma populations were significantly different (all P < 0.05). Conclusions The molecular mutational characteristics of pulmonary adenocarcinoma are complex, and vary greatly among different populations. High throughput sequencing-based multiple-gene detection can reveal its mutational features comprehensively, and that has important roles in personal targeted medication guidance, drug-resistance monitoring and prognosis evaluation. Key words: Lung neoplasms; Adenocarcinoma; High-throughput nucleotide sequencing; Mutation; Molecular targeted therapy

The genetic characteristics of BCR-ABL-negative myeloproliferative neoplasms

Objective: To explore the relationship between driver gene mutation (JAK2, MPL and CALR) and disease type in BCR-ABL negative myeloproliferative neoplasms (MPNs) including primary myeloid fibrosis (PMF), essential thrombocytosis (ET) and polycythemia vera (PV). Methods: A total of 32 MPN related genes were detected by high-throughput sequencing in 156 MPN patients. The relationships between disease type and patients' general performance, the characteristics of driver gene mutations, concomitant gene mutations were analyzed. Results: In the population with JAK2 V617F positive mutation, the proportion of patients over 60 years old in PMF was higher than that with ET or PV. By high-throughput sequencing, 22 concomitant gene mutations were detected in 46 patients with JAK2, MPL or CALR mutations, including 4 (8.3%) in PV, 20 (29.4%) in ET, and 22 (55.0%) in PMF. DNMT3A mutation was detected only in patients with PV, while splicing factor related genes including SF3B1, SRSF2 and U2AF1 were only accompanied by PMF. According to the variation allele frequency (VAF) value of JAK2 V617F mutation, the VAF value associated with PV was the highest (68.15%), followed by PMF (37.7%) and ET (23%). However, there were significant differences in the incidence of JAK2 V617F homozygous among 3 different diseases. In patients with JAK2 mutation, the proportion of other gene mutations in PV and ET was significantly lower than that in PMF. Conclusions: Under the condition of common driver gene mutations (JAK2, MPL and CALR), patients' age, VAF value and homozygous state, concomitant gene mutations are closely related to different disease type. These correlations help to improve clinical understanding of disease characteristics and risk assessment.

Clinical Characteristics of Peripheral Hemogram and DNMT3A Gene Mutation in Patients with Primary AML Treated by FLT3-ITD-mt and FLT3-ITD-wt

To explore the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of relapsed or refractory peripheral T-cell lymphoma(PTCL). The clinical data of 6 patients with relapsed or refractory PTCL undergoing allo-HSCT from Sep. 2014 to Sep. 2018 in the department of hematology, aerospace center hospital were retrospectively analyzed. Complications and disease-free survival after HSCT were observed. All the patients could well tolerate the conditioning regimen and acquired hematopoietic recon-struction. Following up till December 2018, with a median time of 11.5 months (1-51); acute GVHD developed in 2 cases and chronic GVHD developed in 5 cases, Among 6 cases one case died of viral pheumonia and the other 5 patients remained disease-free survival. The longest disease-free survival time has reached 51 months. allo-HSCT is a safe and effective method for relapsed or refractory peripheral T-cell lymphoma, which can be chosen as salvage treatment method for patients with primary resistance. Optimization of the conditioning regimen may result in better efficacy of allo-HSCT.

Clinical Characteristics of Peripheral Hemogram and DNMT3A Gene Mutation in Patients with Primary AML Treated by FLT3-ITD-mt and FLT3-ITD-wt

To explore the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of relapsed or refractory peripheral T-cell lymphoma(PTCL). The clinical data of 6 patients with relapsed or refractory PTCL undergoing allo-HSCT from Sep. 2014 to Sep. 2018 in the department of hematology, aerospace center hospital were retrospectively analyzed. Complications and disease-free survival after HSCT were observed. All the patients could well tolerate the conditioning regimen and acquired hematopoietic recon-struction. Following up till December 2018, with a median time of 11.5 months (1-51); acute GVHD developed in 2 cases and chronic GVHD developed in 5 cases, Among 6 cases one case died of viral pheumonia and the other 5 patients remained disease-free survival. The longest disease-free survival time has reached 51 months. allo-HSCT is a safe and effective method for relapsed or refractory peripheral T-cell lymphoma, which can be chosen as salvage treatment method for patients with primary resistance. Optimization of the conditioning regimen may result in better efficacy of allo-HSCT.

Whole-Exome Sequencing Characterized the Landscape of Somatic Mutations and Pathways in Colorectal Cancer Liver Metastasis.

Purpose Liver metastasis remains the leading cause of cancer-related mortality in colorectal cancer. The mechanism of occurrence and development of liver metastasis from colorectal cancer is unclear. Methods The primary tumor tissues and blood samples of 8 patients with liver metastasis of colorectal cancer were collected, followed by nucleic acid extraction and library construction. Whole-exome sequencing was performed to detect the genomic variations. Bioinformatics was used to comprehensively analyze the sequencing data of these samples, including the differences of tumor mutation burden, the characteristics of gene mutations, and signaling pathways. Results The results showed that the top three genes with the highest mutation frequency were TP53, APC, and KRAS. Tumor mutation burden of this study, with a median of 8.34 mutations per MB, was significantly different with The Cancer Genome Atlas databases. Analysis of molecular function and signaling pathways showed that the mutated genes could be classified into five major categories and 39 signaling pathways, involving in Wnt, angiogenesis, P53, Alzheimer disease-presenilin pathway, notch, and cadherin signaling pathway. Conclusions In conclusion, we identified the extensive landscape of altered genes and pathways in colorectal cancer liver metastasis, which will be useful to design clinical therapy for personalized medicine.

Diversity of familial exudative vitreoretinopathy

Familial exudative vitreoretinopathy (FEVR) is a hereditary retinal vascular dysplasia. So far, 6 genes have been found to be associated with FEVR: Wnt receptor Frizzled Protein 4, Norrie's disease, co-receptor low-density lipoprotein receptor-related protein 5, tetraspanin 12, zinc finger protein 408, and kinesin family members 11 genes. Its clinical manifestations, pathological processes and genetic patterns are diverse, and it shows the relationship between gene polymorphism and clinical manifestation diversity. It is characterized by different symptoms between the same individual, the same family, and the same gene mutation; different clinical stages and gene mutation types of parents or unilateral genetic children; different clinical characteristics and gene mutation patterns of full-term and premature infant; combined with other eye disease and systemic diseases; double gene mutations and single gene mutations have different clinical manifestations and gene mutation characteristics. A comprehensive understanding of the different clinical manifestations and diverse genetics of FEVR can provide better guidance for the treatment of FEVR. Key words: Retinal diseases/genetics; Review; Familial exudative vitreoretinopathy

Clinical features and genetic characteristics of myoclonic-atonic epilepsy caused by SLC6A1 gene mutation

Objective To explore the clinical features and genetic characteristics of myoclonic-atonic (MAE) caused by gene mutation. Methods The clinical data of a patient with gene mutation from Xiangya Hospital of Central South University was collected. The related literatures were reviewed from Wanfang Data, China National Knowledge Infrastructure, PubMed (until July 2019) by using keywords SLC6A1 and myoclonic-atonic epilepsy . The characteristics of gene mutation and the clinical phenotype of children with myoclonic-atonic were summarized. Results A 8 year and 8 months old girl was enrolled in the study. Her first attack happened at the age of 19 months, and multiple seizure types including myoclonic-atonic, atonic and absence were observed. The seizures were well controlled by valproate (VPA), but she has mild-moderate intellectual disability. Whole exome-sequencing study identified a de novo nonsense variant of c. 46G>T(p.Glu16*)in gene. A total of 27 cases including the present case with gene mutation were analyzed. 22 mutations were identified, including 11 missense mutations, 5 nonsense mutations, 3 frameshift mutations, 2 splicing mutation and 1 with chromosome microdeletion. Among them 26 patients had more one type of seizures, 20 cases had absence seizures, 17 cases had atonic seizures, 14 cases had myoclonic seizures, 11 cases had myoclonic-atonic seizures, 4 cases had generalized tonic-clonic seizures, 3 cases had eyelid myoclonias, 2 cases had nonconvulsive status epilepticus and 2 cases had tonic seizure. 24 patients had described intelligence assessment. Among them, 18 had developmental delay before onset, 11 had developmental regression after onset. There were 9 cases with autistic features, 4 cases with attention deficit hyperactivity disorder and 3 cases with ataxia. The seizures of 17 cases were controlled, 4 cases had partial seizure control, 3 cases had no significant improvement, and other 3 cases were unclear. Conclusions The main clinical feature of MAE patients with gene mutations is absence and atonic seizures, cognition before onset can be impaired, and some patients had behavioral problems, such as autistic features or attention deficit hyperactivity disorders. VPA is recommend as first-line treatment. Key words: Epilepsies, myoclonic; Epilepsy, absence; Glucose transporter type 1; Mutation; Child

Hyperglycemia caused by mutation of GCK gene in 10 patients analysis of clinical and mutation characteristics

Objective: To explore the gene mutation characteristics and detailed clinical presentations of hyperglycemia caused by GCK mutations in 10 patients. Methods: The clinical and follow-up data of 10 patients with hyperglycemia caused by mutation of GCK gene were reviewed. The patients were ascertained between January 1, 2014 and August 31, 2018 at the Department of Pediatrics, the First Affiliated Hospital of Zhejiang University and Ningbo Women & Children's Hospital. Clinical data were collected, including age, gender, main complaint, family history, fasting blood glucose, fasting blood insulin, 2-hour blood glucose, 2-hour blood insulin after oral glucose tolerance test, glycosylated hemoglobin, anti-glutamic acid decarboxylase antibody and body mass index. Mutations of GCK gene were detected by Sanger sequencing or high-throughput sequencing of diabetes-related genes in the patients and their family members. Results: There were ten patients, 8 of them were male, 2 were female.The ages at diagnosis varied between 4.7 to 12.3 years. The patients usually did not have obvious clinical symptoms of diabetes mellitus. Most of them were unexpectedly found to have hyperglycemia and with impaired glucose metabolism in three consecutive generations. The fasting blood glucose of patients was 6.8-7.7 mmol/L, 2-hour postprandial blood glucose was 7.8-11.6 mmol/L. Fasting blood insulin was 0.5-8.5 mU/L, glucose tolerance test results showed that 2 h postprondial blood insulin was 1.3-55.4 mU/L. The level of glycosylated hemoglobin was 6.1%-6.8%. Anti-glutamic acid decarboxylase antibody was negative in all patients. The GCK mutations identified in patients and one of their parents were located at exon5 (4 cases), exon9 (2 cases), exon2 (1 case), exon4 (1 case), exon6 (1 case) and exon7 (1 case). Conclusions: Most of the hyperglycemia patients caused by GCK mutations did not have typical clinical symptoms of diabetes. The fasting blood glucose was slightly elevated. Abnormal glucose tolerance test results were found in all 10 patients. Three consecutive generations of family had impaired glucose metabolism. GCK mutations located at exon 5 were common in 10 cases. There was no correlation between type of mutations and plasma glucose levels in domestic and international researches. When fasting glucose was found abnormal in clinic, a complete family history should be taken and the GCK gene should be sequenced to confirm the diagnosis in time.

Carnitine-acylcarnitine translocase deficiency with homozygous mutation of c.199-10T>G: a case report and literature review

Objective To investigate the clinical features of carnitine-acylcarnitine translocase deficiency (CACTD) with c.199-10T>G homozygous mutation and the characteristics of SLC25A20 gene mutation. Methods This study retrospectively analyzed the clinical data, biochemical and genetic features, treatment and outcome of a boy with CACTD with c.199-10T>G homozygous mutation, who admitted to Guangzhou Women and Children's Medical Center in September 2017. Pertinent articles were retrieved from China National Knowledge Infrastructure (CNKI), Wanfang Database, National Center for Biotechnology Information and PubMed from the establishment of these databases to April 2018 using key words including CACT, SLC25A20 and carnitine-acylcarnitine translocase. Clinical information of all affected cases in the retrieved publications was analyzed. Results (1) The full-term boy born vaginally at a local hospital was transferred to neonatal intensive care unit (NICU) of Guangzhou Women and Children's Medical Center at 2 days and 5 hours due to groaning, cyanosis and severe hypoglycemia (0.8 mmol/L) at 15 h after birth. His elder brother with similar symptoms died of unknown reason at 50 days of age. In this case, ammonemia, liver enzyme and creatine kinase were significantly elevated, amino acid analysis suggested liver damage, and high amounts of dicarboxylic aciduria, low free carnitine, markedly increased long-chain acylcarnitine and hypoketotic hypoglycemia were also observed. His electrocardiogram showed atrioventricular block and ventricular tachycardia. After a series of treatments, including repeated electrical cardioversion, lidocaine and amiodarone for arrhythmia, arginine for blood ammonia level reduction, formula supplement containing L-carnitine and medium-chain fatty acid, the patient whose conditions had significantly improved and was discharged at the request of his parents at 29 days old. Two weeks later, he was re-admitted due to diarrhea, and discharged two days later when he was 45 days old. He was lost to follow up since then. (2) A homozygous mutation of c.199-10T>G was detected in this boy in SLC25A20 gene, which was also carried by his parents. (3) Thirty-two publications in English were retrieved, involving 50 cases of CACTD and 100 sequenced alleles. A total of 40 mutations in SLC25A20 gene were found so far, and c.199-10T>G was the most common mutation with a frequency of 22/100. It was identified in 13 patients, including nine homozygous mutations and four compound heterozygous mutations. Symptoms presented within 72 h after birth (25 min-52 h) in all the 13 infants, such as hypoketotic hypoglycemia, hyperammonemia, elevated liver enzyme and creatine kinase, significantly decreased free carnitine level, markedly increased level of long-chain acylcarnitine, dicarboxylic aciduria, arrhythmia and cardiomyopathy. The mortality rate of CACTD was 11/12 (the outcome of one case was not reported). Conclusions c.199-10T>G is the most common SLC25A20 gene mutation reported in Asia population with severe phenotypes and poor outcomes. Early diagnosis and timely treatment of CACTD are crucial. Inborn metabolic diseases such as CACTD should be considered if unexplainable exacerbation of clinical signs in neonatal period, or sudden infant death occurs. Key words: Carnitine acyltransferases; Lipid Metabolism, Inborn Errors; Membrane transport proteins; Mutation

NPM1 High Mutant Allele Burden is an Adverse Prognostic Factor for AML Patients with Mutated NPM1

To investigate the clinical features, accompanying gene mutation characteristics and prognostic factors of adult patients with acute myeloid leukemia with mutated NPM1 (NPM1+AML). Seventy-three patients with newly diagnosed adult NPM1+AML were selected. The mutations of 22 genes were detected by second generation sequencing and 43 fusion genes of AML were detected by real-time fluorescent quantitative PCR. The Kaplan-Meier survival curve and Cox multivariate regression analysis were used to study the prognostic factors. A total of 74 NPM1 site mutations were detected in 73 patients with NPM1+AML. The incidence rates were 92.0% L287fs, 2.7% Q289fs and W288fs, 1.4% L258fs and Q289H, among which 1 patient had 2 NPM1 mutations; the different mutation sites had no effect on the prognosis of NPM1+AML. The median value of NPM1 variant allele frequency (VAF) was 35.4% (1.8%-56.6%). Based on the uppermost quartile of 38.4%, the patients were classified as NPM1 VAF>38.4% (NPM1highAML) and NPM1 VAF≤38.4% (NPM1lowAML). Compared with NPM1lowAML, the early mortality rate was statistically significantly higher (33.3% vs 7.3%, P<0.05), and median EFS (148 d，95%CI 58-238 d vs 372 d，95%CI 264-480 d) (P<0.01) and median OS (179 d 95%CI 6-352 d vs 444 d) (P<0.01) were significantly shorter in NPM1high AML. A total of 126 accompanying gene mutation sites were detected in 87.7% of patients with NPM1+AML. The patients with NRAS gene mutation displayed a higher rate of complete remission (100% vs 58%) (P<0.05) and longer median OS (not reached to 320 d, 95%CI 150-490 d) (P<0.05). The 43 fusion genes were examined in 65 out of 73 cases of NPM1+AML, and in all the patients the fusion gene test was negative. Multivariate analysis showed that NPM1 VAF>38.4% was an independent prognostic factor for EFS (HR=3.1, 95% CI 1.6-6.4, P<0.01) and OS (HR=3.0, 95% CI 1.4-6.2, P<0.01). The NPM1 gene mutation in AML patients often is accompanied by other gene mutations, while the coexistence of fusion genes is rare; high NPM1 mutant allele burden is an independent prognostic factor for adult AML patients with mutated NPM1.

Mutation spectrum and new mutation of phenylalanine hydroxylase gene in Guangxi region

Objective To investigate the characteristics of the phenylalanine hydroxylase(PAH) gene mutations in patients with phenylketonuria(PKU) in Guangxi region, in order to provide clinical data for genetic counseling and prenatal gene diagnosis. Methods Thirty-seven children diagnosed as PKU in the Maternal and Children′s Hospital of Guangxi Zhuang Autonomous Region were enrolled in the study between January 2009 and December 2017. Venous blood was collected and the PAH gene sequence was determined by Sanger sequencing after amplification with the polymerase chain reaction technique. The new gene mutations were defined based on the national and international literature review and databases.Meanwhile, 100 healthy individuals were selected as the control group for gene sequencing to confirm whether the mutation was a new one. Results Thirty-seven cases of PKU were detected for 68 mutations, with the detection rate being 91.89% (68/74). Six mutations were identified in exon 7, which accounted for 31.08% of all, exon 12(18.92%), exon 8(10.81%) and exon 6 (10.81%) followed.A total of 25 different mutations were identified which including 14 missense mutations(56.00%), 7 nonsense mutations(28.00%), 3 splicing junction mutations(12.00%), and 1 deletion mutation(4.00%). The most common mutations included c. 1223G>A(p.R408Q), c.728G>A(p.R243Q) and c. 721C>T(p.R241C), accounting for 14.86%, 13.51%, and 10.81%, respectively.After querying international databases, including PAH mutation database and Human Gene Mutation Database and forecasting software, three kinds of mutations c. 314C> T (p.T105I), c.583A> G (p.K195E), c .851G> A(p.C284Y) were verified as novel PAH gene mutations. Conclusions The mutation spectrum of the PAH gene in Guangxi has been identified.And 3 kinds of mutations have been identified.This may accumulate valuable information for gene diagnosis and prenatal diagnosis of PKU in Guangxi region. Key words: Phenylketonuria; Phenylalanine hydroxylase; Gene mutation

Analysis of gene mutation characteristics in patients with chronic neutrophilic leukaemia

ABSTRACTObjective: This study aims to investigate the gene mutation characteristics of chronic neutrophilic leukaemia (CNL).Method: This study retrospectively analyses the molecular biological characteristics, laboratory characteristics and clinical data of four patients with CNL that were admitted in the second Hospital of Shanxi Medical University from May 2014 to October 2016. On the basis of the molecular biological data of 22 patients with CNL and 4 patients with CNL, we further analysed the characteristics of CNL molecular mutation.Results: Two out of the four patients with CNL were carriers of colony-stimulating factor 3 receptor (CSF3R) mutation, among which two were carriers of CSF3R T618I mutation combined with ASXL1 mutation and SETBP1 mutation, and two were only carriers of JAK2 V617F mutation. According to the molecular biological data of 22 patients with CNL, 20 patients were positive for CSF3R mutation. Two patients were positive for JAK2 V617F mutation. A total of 10 patients were positive for SETBP1 mutation which was correlated with the CSF3R T618I gene mutation (P = 0.03). A total of 13 patients were positive for ASXL1 mutation. No patients carried mutations in ASXL2 and MPL genes.Conclusion and Discussion: CSF3R mutation is the main tumorigenic mutation in CNL, in which CSF3R T618I mutation is the main mutation, and an extremely small number of CNL patients may be caused by JAK2 V617F mutation. SETBP1 and ASXL1 are the most common concomitant mutations in CNL with CSF3R mutation, and SETBP1 and CSF3R T618Imutations may have a certain correlation.

Ratio of JAG1 and NOTCH2 gene mutation characteristics in children with alagille syndrome at Children's hospital 1 in Ho Chi Minh city, Vietnam

Background: The early diagnosis of ALGS is crucial because the disease is often a variable expression, and the symptoms are similar to other pathologies, especially biliary tract atrophy. The primary objective of this study was determined of the ratio of JAG1 and NOTCH2 gene mutation characteristics in children with Alagille syndrome (ALGS). Methods: Batch description of the cases was performed on 32 pediatric patients with ALGS treated at Childrend’s Hospital 1 from February 2015 to December 2018. Results: Based on the study of 32 children with ALGS, the following results were obtained: The JAG1 gene mutation detection rate is 75%; No instances of NOTCH2 gene mutation were detected. The meaningless mutation rate was 33%, the false means was 29%, the split frame was 21%, the cutting connector was 13%, and the loss of the small segment was 4%. Mutations were distributed on most exons, and the surge screening ratio of JAG1 patient’s relatives with mutations was 23.5%. Conclusion: Results indicated that early diagnosis of ALGS based on JAG1 or NOTCH2 mutations is possible. How to Cite this Article Pubmed Style Tram Van Ta, Tuan Anh Nguyen, Truong Viet Nguyen. of JAG1 and NOTCH2 gene mutation characteristics in children with alagille syndrome at Children’s hospital 1 in Ho Chi Minh city, Vietnam . SRP. 2019; 10(1): 173-178. doi:10.5530/srp.2019.1.32 Web Style Tram Van Ta, Tuan Anh Nguyen, Truong Viet Nguyen. of JAG1 and NOTCH2 gene mutation characteristics in children with alagille syndrome at Children’s hospital 1 in Ho Chi Minh city, Vietnam . http://www.sysrevpharm.org/?mno=302644894 [Access: March 29, 2021]. doi:10.5530/srp.2019.1.32 AMA (American Medical Association) Style Tram Van Ta, Tuan Anh Nguyen, Truong Viet Nguyen. of JAG1 and NOTCH2 gene mutation characteristics in children with alagille syndrome at Children’s hospital 1 in Ho Chi Minh city, Vietnam . SRP. 2019; 10(1): 173-178. doi:10.5530/srp.2019.1.32 Vancouver/ICMJE Style Tram Van Ta, Tuan Anh Nguyen, Truong Viet Nguyen. of JAG1 and NOTCH2 gene mutation characteristics in children with alagille syndrome at Children’s hospital 1 in Ho Chi Minh city, Vietnam . SRP. (2019), [cited March 29, 2021]; 10(1): 173-178. doi:10.5530/srp.2019.1.32 Harvard Style Tram Van Ta, Tuan Anh Nguyen, Truong Viet Nguyen (2019) of JAG1 and NOTCH2 gene mutation characteristics in children with alagille syndrome at Children’s hospital 1 in Ho Chi Minh city, Vietnam . SRP, 10 (1), 173-178. doi:10.5530/srp.2019.1.32 Turabian Style Tram Van Ta, Tuan Anh Nguyen, Truong Viet Nguyen. 2019. of JAG1 and NOTCH2 gene mutation characteristics in children with alagille syndrome at Children’s hospital 1 in Ho Chi Minh city, Vietnam Reviews in Pharmacy, 10 (1), 173-178. doi:10.5530/srp.2019.1.32 Chicago Style Tram Van Ta, Tuan Anh Nguyen, Truong Viet Nguyen. Ratio of JAG1 and NOTCH2 gene mutation characteristics in children with alagille syndrome at Children’s hospital 1 in Ho Chi Minh city, Vietnam . Systematic Reviews in Pharmacy 10 (2019), 173-178. doi:10.5530/srp.2019.1.32 MLA (The Modern Language Association) Style Tram Van Ta, Tuan Anh Nguyen, Truong Viet Nguyen. Ratio of JAG1 and NOTCH2 gene mutation characteristics in children with alagille syndrome at Children’s hospital 1 in Ho Chi Minh city, Vietnam . Systematic Reviews in Pharmacy 10.1 (2019), 173-178. Print. doi:10.5530/srp.2019.1.32 APA (American Psychological Association) Style Tram Van Ta, Tuan Anh Nguyen, Truong Viet Nguyen (2019) of JAG1 and NOTCH2 gene mutation characteristics in children with alagille syndrome at Children’s hospital 1 in Ho Chi Minh city, Vietnam Reviews in Pharmacy, 10 (1), 173-178. doi:10.5530/srp.2019.1.32

New mutation of ACADVL-related very long chain acyl-CoA dehydrogenase deficiency

Objective According to the clinical and gene mutation characteristics of ACADVL-related very long chain acyl-CoA dehydrogenase deficiency(VLCADD), the types that contribute to the gene mutation of were summarized. Methods By analyzing clinical, laboratory and genetic data of 1 case with ACADVL-related very long chain acyl-CoA dehydrogenase deficiency diagnosed from Department of Pediatrics, the Affiliated Hospital of Inner Mongolia Medical University in August 2016, based on the agreement signed by both the little patient′s parents and the hospital, plus the high-throughput sequencing analysis and PCR sequencing test for the 2 generation genes, some presented mutation sites were analyzed and concluded, in addition to taking ACADVL as key words to search the databases from CNKI, Wanfang(updated in 2016) as well as PubMed and related documents from On-line Mendal Inheri-tant databases of Man(OMIM) and HGMD. Results Through physical examination, VLCADD was diagnosed.After being given Levocamitine and the diet likemedium-chain fatty acid food for a week, the metabolism returned to normal.Tracking him for 3 months, his hepatitis obviously rebounded, within the reach of 3 cm under the right rib and 1 cm under the xiphoid.The exome sequencing study (trios) was identified the novel heterozygous mutation according to the statistics below ACADVL(NM_000018.3) Exon7: c.608C>T; p.(Pro203Leu)(heterozygous)and ACADVL(NM_000018.3) Exon18: c.1748C>T; p.(Ser583Leu)(heterozygous) in ACADVL.Relevant literature reported suggest these two mutations from both the parents are pathogenic genes, which can account for the reason why the boy got ill.However, these two mutations had not been reported in ACADVL-related VLCADD so far.Up to now, 73 types of mutations from documents index were related to the VLCADD, but the clinical case included 75 kinds of gene mutations. Conclusions The apparent symptoms of the boy with the gene mutation were reflected in abnormal heart rates, hepatomegaly and hypoglycemia.VLCADD was diagnosed through genetic testing, and systematic treatment can partly control the development of the disease.In conclusion, the findings(exon 7 and 18) show that according to the genetic tests, disease-causing genes from both parents are new mutations of and they are pathogenic. Key words: Very long chain acyl-CoA dehydrogenase deficiency; ACADVL; Mutation

Analysis of clinicopathological characteristics of papillary thyroid carcinoma and BRAF V600E gene mutation

Objective: To study the correlation between the BRAF V600E mutation and the clinicopathological features of papillary thyroid carcinoma(PTC), and to explore the application value of BRAF V600E mutation in PTC. Method: The BRAF V600E gene mutation was detected in 108 PTC cases and 30 control cases by qPCR. The results were statistically analyzed by using SPSS 21.0 software. Result: The BRAF V600E mutation was absent in the control group. The BRAF V600E mutation rate was 72.20% in 108 PTC cases. Compared with patients with wild type,the mean age of patients with the mutant BRAF V600E was significantly older(P<0.05). BRAF V600E mutations were associated with PTC tissue subtypes and central area lymph node metastasis(P<0.05). BRAF V600E mutations were not correlated with tumor diameter, patient gender, multifocality, tumor site, concomitant disease, lymph node metastasis in side region of neck, capsule invasion, and TNM staging(P>0.05). Conclusion: The value of BRAF V600E mutation in the prognosis of PTC remains to be studied. BRAF V600E mutation is of value for pathological diagnosis of PTC.