Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 556
Filter
1.
Acta Pharmaceutica Sinica ; (12): 2024-2031, 2022.
Article in Chinese | WPRIM | ID: wpr-936559

ABSTRACT

Cystic fibrosis (CF) is a common and life-threatening autosomal recessive disorder in Caucasians populations. The disease is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The absence of mature CFTR at the correct cellular location or dysfunction of CFTR proteins has been observed in CF patients. CF is frequently accompanied by a variety of complex complications, such as impairments in pulmonary functions, which may lead to successive infections and respiratory failure. Recently, with the understanding of the pathogenesis of CF, a wide array of therapeutic strategies for the treatment of CF has been designed. This review summarizes pathogenic mechanisms of CF, mechanisms of action of drugs, routes of administration, and new drug development as well as provides insights into the advanced treatment strategies for CF.

2.
Article in Chinese | WPRIM | ID: wpr-934988

ABSTRACT

Objective@#To detect WNT10A gene mutations in patients with oligodontia or anodontia (≥6 teeth missing) and analyze their dental phenotype. @*Methods@#Patients with oligodontia or anodontia were enrolled from the clinic for oral examination, genetic history collection and whole exon sequencing, and patients with WNT10A gene mutations were included. Sanger sequencing was utilized to validate the WNT10A gene variations in probands and family members compared with the normal sequence. The pathogenicity of WNT10A mutations was evaluated by functional prediction, conservation analysis and structure prediction of protein mutants. Implant rehabilitation was applied to restore the patients' oral function.@*Results@# Five WNT10A gene mutations were detected in six unrelated patients, and c.26G>A (p. Trp9X) and c.1036delT (p. Cys346fs) were novel mutations with pathogenic potential. The mean number of missing teeth was (15.33±8.64) per case. The most frequently missing permanent teeth were maxillary canines (100%), and the least frequently missing teeth were mandibular first molars (25%). Implant rehabilitation was applied in five patients, and patients were found to have ideal implant osseointegration and functional restoration.@*Conclusion @# This study identified novel WNT10A gene pathogenic variants, enriching the WNT10A gene spectrum and providing new evidence for genetic diagnosis and prenatal consultation. Implant rehabilitation was also proven to be a treatment option for these patients.

3.
Cancer Research and Clinic ; (6): 39-42, 2022.
Article in Chinese | WPRIM | ID: wpr-934624

ABSTRACT

Objective:To investigate the clinical characteristics of non-small cell lung cancer (NSCLC) patients with different epidermal growth factor receptor (EGFR) gene mutations and the comparison of therapeutic effects.Methods:The clinical data of 324 patients with NSCLC admitted to the 904th Hospital of the Joint Service Support Force of PLA from April 2018 to June 2020 were retrospectively analyzed. Gene sequencing method was used to detect EGFR gene and mutations of exons 19 and 21. NSCLC patients with EGFR gene mutations were divided into group A (mutation of exon 19 of EGFR gene) and group B (mutation of exon 21 of EGFR gene). Both groups were treated with gefitinib combined with TP (paclitaxel + cisplatin) regimen for 3 months. The clinical features, efficacy and adverse reactions of the two groups were compared.Results:Among 234 NSCLC patients, 107 cases (45.73%) had EGFR gene mutations. Among them, there were 49 cases in group A (including delE746-A750 mutation in 32 cases, delL747-P753insS 3 mutation in 8 cases, delL747-A750 1 mutation in 6 cases, delL747-T751 1 mutation in 3 cases), and there were 58 cases in group B (all L858R mutations), and no double mutations in exons 19 and 21 were found in both groups. There were no significant differences in gender, TNM staging, pathological type, smoking history, age, degree of differentiation, tumor location, tumor diameter, and lymph node metastasis in the two groups (all P > 0.05). The difference in the clinical control rates of group A and group B was not statistically significant [91.8% (45/49) vs. 89.7% (52/58), χ2=0.15, P = 0.699]. The incidence of grade Ⅲ-Ⅳ adverse reactions in the two groups during treatment had no statistically significant differences (all P > 0.05). Conclusions:EGFR mutation rate in NSCLC patients is relatively high, most of which are EGFR exons 19 and 21 mutations. Gefitinib combined with TP regimen in the treatment of EGFR exons 19 and 21 mutations in NSCLC patients has good curative effects and high safety.

4.
Article in Chinese | WPRIM | ID: wpr-934406

ABSTRACT

Objective:To investigate the diagnostic value of fluorescence quantitative method and G6PD/6PGD ratio method in glucose-6-phosphate dehydrogenase (G6PD) deficiency and the type of gene mutation.Methods:A total of 1 201 patients (711 males and 490 females) with suspected G6PD deficiency in Shanghai Children′s Hospital were collected from June 2018 to March 2021. Fluorescence quantification method, G6PD/6PGD ratio method and multicolor melting curve were used to detects enzyme activity, ratio and gene mutation type. Comparison of each index and evaluation of its diagnostic efficiency were performed.Results:Among 1 201 suspicious samples, 163 cases (135 males and 28 females) were finally diagnosed. 156 cases were diagnosed by fluorescence quantitative method with a detection rate of 95.71%, and 140 cases were diagnosed by G6PD/6PGD ratio method with a detection rate of 85.89%. enzymatic activity of G6PD and ratio of G6PD/6PGD in male were significantly lower than female, and the differences were statistically significant ( U=642.5, 734.5, P<0.001). 112 cases received G6PD gene mutation detection and 92 cases were diagnosed, 74 were hemizygous mutations, 1 were homozygous mutations, 15 were heterozygous mutations, and 2 were compound heterozygous mutations. Among 15 cases of heterozygous mutations, 11 cases were diagnosed by fluorescence quantitative method, the diagnosed rate was 73.33%, 4 cases were diagnosed by G6PD/6PGD ratio method, and the diagnosed rate was 26.67%. A total of 7 mutation sites were detected and the proportions were c.1388G>A (32.22%), c.1376G>T (30.00%), c.871G>A (13.33%), c.1024C>T (11.11%). c.95A>G (7.78%), c.487G>A (4.44%), c.392G>T (1.11%). The enzymatic activities of c.1376G>T and c.1024C>T, c.487G>A were statistically significant ( P<0.001,0.015); the G6PD/6PGD ratios of c.1024C>T and c.1388G>A, c.1376G>T were statistically significant ( P=0.017,0.002,0.011,0.013). Fluorescence quantitative method had sensitivity of 100%, specificity of 95.65%, and the area under the curve (AUC) is 0.972. The sensitivity of the G6PD/6PGD ratio method was 100%, the specificity was 94.57%, and the AUC was 0.979. The sensitivity of fluorescence quantitative method combined with G6PD/6PGD ratio was 96.7%, the specificity was 100%, and the AUC was 0.992. Conclusions:Compared with fluorescence quantification, the G6PD/6PGD ratio method might not be able to diagnose female heterozygotes effectively; The panel of G6PD fluorescence quantification and G6PD/6PGD ratio was helpful to reduce the missed diagnosis. Combined with gene mutation analysis, it could improve the diagnosis rate of G6PD deficiency in the children.

5.
Article in Chinese | WPRIM | ID: wpr-934401

ABSTRACT

Objective:To investigate the molecular pathogenesis of a newly discovered gene mutation in a family with hereditary coagulation factor Ⅺ(FⅪ) deficiency.Methods:The proband was admitted to the First Affiliated Hospital of Wenzhou Medical University in September 2021 due to "calculus of intrahepatic duct". The patient had no symptoms of spontaneous bleeding.The clinical data and blood samples of the proband and her family members (10 persons in 3 generations) were collected.The activated partial thromboplastin time (APTT) and FⅪ activity (FⅪ:C) were performed by the one-stage clotting assay. FⅪ antigen (FⅪ:Ag) were detected by enzyme linked immunosorbent assay (ELISA). Genomic DNA extracted from peripheral blood cells of subjects was used as template to analyze F11 gene mutation by DNA direct sequencing. Bioinformatics software was used to analyze the effects of mutations on protein structure and function. Wild-type and mutant FⅪ protein expression vectors were constructed and transient transfected into HEK293T cells. The total RNA was extracted from positive transfected cells and then reversely transcribed into cDNA. The mRNA expression level of F11 gene in transfected cells was detected by real-time fluorescence quantitative PCR (qRT-PCR). The content of FⅪ:Ag and the expression of FⅪ protein in transfected cell lysates and culture supernatant were detected by ELISA and western blot.Results:The APTT of the proband was significantly prolonged to 107.9s (reference range 29.0-43.0s), while FⅪ:C and FⅪ:Ag were significantly decreased to 2% (reference range 84%-122%) and 5% (reference range 76%-127%), respectively. Gene sequencing analysis indicated that the proband had c.536C>T (p.Thr161Met) heterozygous missense mutation and c.1556G>A (p.Trp501Ter) heterozygous nonsense mutation in exon 6 and 13 of the F11 gene, respectively. Bioinformatics analysis showed that the amino acids at site 161 of FⅪ protein were threonine (Thr) in the matrix composed of five different species, indicating that Thr161 site was highly conserved among homologous genes in different species. p.Thr161Met heterozygous mutation affected the stability of local intermolecular structure of FⅪ protein. In vitro expression experiments of p.Thr161Met mutation showed that FⅪ protein had a normal synthesis in the cells but secretion dysfunction.Conclusions:c.536C>T (p.Thr161Met) heterozygous missense mutation and c.1556G>A (p.Trp501Ter) heterozygous nonsense mutation were mainly responsible for the decrease of FⅪ in this family. p.Thr161Met mutation was first reported in the world and did not affect the normal synthesis of FⅪ protein, but caused secretion dysfunction.

6.
Article in Chinese | WPRIM | ID: wpr-934363

ABSTRACT

Objective:To study the clinical and molecular characteristics of a family with familial hypercholesterolemia (FH) with LDLRAP1 and ABCG8 gene abnormality.Methods:In September 2020, one case of FH was included in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine; peripheral venous blood samples of members of the family were collected to detect serum total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) indicators; use high-performance liquid chromatography to detect serum stigmasterol and sitosterol content; perform second-generation gene sequencing to detect gene mutations in probands and family members; use Pymol software to detect gene mutations point for pathogenicity analysis, and use Uniprot Modelling software to perform protein structure modeling.Results:The patient presented with anemia, multiple xanthomas and early-onset acute coronary syndrome. The coronary angiography showed severe coronary artery lesions; abdominal ultrasound showed splenomegaly; blood smear showed shaped erythrocytes and large platelets. The level of serum TC, LDL-C, stigmasterol and sitosterol was 8.54 mmol/L (2.3-5.7 mmol/L), 4.84 mmol/L (range of normal value 1.3-4.3 mmol/L), 44 μmol/L (1.0-10 μmol/L), 28 μmol/L (1.0-15 μmol/L), respectively; LDLRAP1 gene mutation was found: exon4 c.415C>T:p.Q139X; the truncated protein formed by this homozygous mutation lost multiple stable protein structure regions, which can not have a normal function. At the same time, ABCG8 gene mutations were also found: exon13 c.1895T>C (p.V632A) and exon8 c.1199C>A:p.T400K . Two cases of family members had a mild increase in HDL-C (Ⅱ5: 2.33 mmol/L, Ⅱ6∶2.96 mmol/L), 3 cases carrying the ABCG8 gene mutations had a slight increase in stigmasterol (Ⅱ8: 23 μmol/L, Ⅱ7: 24 μmol/L, Ⅰ2: 18 μmol/L) and sitosterol (Ⅱ8: 41 μmol/L, Ⅱ7: 33 μmol/L, Ⅰ2: 45 μmol/L), suggesting that its association with the concentration of plant sterols. Conclusions:FH patients with LDLRAP1 and ABCG8 gene abnormalities may have abnormal plant sterol concentrations, and their clinical manifestations are more complicated. Therefore, family history, LDL-C, plant sterol levels, and genetic test results should be considered comprehensively.

7.
Article in Chinese | WPRIM | ID: wpr-933749

ABSTRACT

With the advances in molecular genetic techniques, especially next-generation sequencing technologies, genetic testing is now a widely applied procedure in diagnosing hereditary muscle diseases. However, there remain many challenges to assessing the pathogenicity of genetic variants, understanding disease pathogenesis, and developing therapeutic strategies in hereditary muscle diseases. The zebrafish model system is a powerful tool to address these issues, thanks to conserved vertebrate genetics, the ease of genetic manipulation, and various assessment approaches for muscle function. Given the limited use of zebrafish model organisms on muscle disease research in China, this article mainly focuses on the advantages, applications, and limitations of zebrafish as a model of hereditary muscle disease.

8.
Article in Chinese | WPRIM | ID: wpr-933498

ABSTRACT

Objective:To explore genetic etiology and evaluate antifungal immunity in a patient with recurrent cervical lymphadenitis caused by Candida albicans. Methods:Next-generation sequencing was performed to screen susceptibility genes for mycosis in a patient with recurrent cervical lymphadenitis caused by Candida albicans and his parents. Peripheral blood mononuclear cells (PBMCs) and neutrophils were extracted from the patient and 6 healthy controls, and subjected to in vitro co-culture with Candida albicans. Western blot analysis was performed to determine the expression of caspase recruitment domain-containing protein 9 (CARD9) in PBMCs of the patient, enzyme-linked immunosorbent assay to detect levels of tumor necrosis factor-α (TNF-α), interleukin (IL) -6, IL-17A, IL-1β and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the co-culture medium, and a colony-counting method was used to detect the survival rate of Candida albicans after treatment with neutrophils. Statistical analysis was carried out by using t test for comparisons between two groups. Results:Two compound heterozygous mutations were identified in the CARD9 gene of the patient, including c.68C>A (p.S23X) in exon 2 inherited from his father and c.820dupG (p.D274Gfs*61) in exon 6 inherited from his mother. Western blot analysis showed that the relative expression level of CARD9 protein in the PBMCs was 0.41 ± 0.07 in the healthy control group, but CARD9 expression was absent in the patient. After stimulation with heat-inactivated Candida albicans spores, the levels of TNF-α, IL-6, IL-17A, IL-1β and GM-CSF secreted by PBMCs of the patient were significantly lower than those by PBMCs of the healthy controls (all P < 0.001). After 30- and 120-minute in vitro co-culture with neutrophils, the survival rates of Candida albicans were significantly higher in the patient (78.00%, 74.00%, respectively) than in the healthy controls (70.91% ± 1.75%, 34.55% ± 5.35%, t = 3.74, 6.99, respectively, both P < 0.05) . Conclusion:Compound heterozygous mutations were identified in the CARD9 gene of the patient with recurrent cervical lymphadenitis caused by Candida albicans, which led to the absence of CARD9 protein expression, and the patient had a defect in the immunity against Candida albicans.

9.
Article in Chinese | WPRIM | ID: wpr-933443

ABSTRACT

Objective:To explore the clinical phenotype and genotype of a family with hereditary hypofibrinogenemia.Methods:Activated partial thrombin time (APTT), prothrombin time (PT),thrombin time (TT) and thrombelastogram (TEG) were tested in all family members. Fibrinogen activity and antigen were detected by Clauss method and immunoturbidimetric method respectively. All exons and flanking sequences of fibrinogen FGA,FGB,FGG genes were analyzed by PCR, and the products were subjected to Sanger sequencing.Results:The proband represented prolonged PT and TT, low Fg activity and antigen, elevated K value and decreased Angle value in TEG. Other family members reported similar changes including proband′s father,daughter and son, and his elder brother and his niece. Exon 5 c.510_512 of FGG gene in the proband revealed a minor deletion mutation.Conclusion:The novel heterozygous missense mutation of exon 5 c.510_512del (Gln170_Ile171 del ins His) of FGG gene is the molecular mechanism that leads to hereditary hypofibrinogenemia in this family.

10.
Article in Chinese | WPRIM | ID: wpr-933384

ABSTRACT

A case of familial hypocalciuric hypercalcemia type 1 (FHH1) was reported detailing the course of diagnosis and treatment. The main clinical manifestations of the patient were recurrent pancreatitis with moderate hypercalcemia and low urinary calcium. The C→T heterozygous missense mutation at nucleotide 2 393 with conversion of codon Pro798 to Leu (p.P155L) in CaSR gene was identified. Serum calcium and parathyroid hormone levels of the patient were decreased significantly after treatment with cinacalcet.

11.
Article in Chinese | WPRIM | ID: wpr-933380

ABSTRACT

Kallmann syndrome(KS) is a subtype of idiopathic hypogonadotropic hypogonadism(IHH), characterized by delayed puberty, undeveloped secondary sexual characters, accompanied by anosmia, or hyposmia. At present, more than 40 genes are related to the pathogenesis of IHH, and new gene loci have been found continuously. At the same time, digenic gene mutation or oligogenic mutation is considered to be an important pathogenic mechanism of IHH. The clinical phenotype of KS/IHH caused by different gene mutations is complex and diverse, and the response to treatment is also variable. This paper presents the clinical data and treatment of a case of KS caused by a compound double heterozygous mutation of WDR11 and PROKR2 genes. PROKR2 gene is a classic KS pathogenic gene, while the WDR11 gene is a relatively new type of KS pathogenic gene. Included with this case report is a literature review of characteristics of cases with WDR11 gene mutation.

12.
Article in Chinese | WPRIM | ID: wpr-930488

ABSTRACT

Objective:To summarize the clinical manifestations of a case of combined oxidative phosphorylation deficiency 28 (COXPD-28) caused by the mutations of the SLC25A26 gene, thus providing references for the diagnosis and genetic counseling of the disease. Methods:Clinical data of a case of COXPD-28 treated in the Third Affiliated Hospital of Zhengzhou University in October 2020 were retrospectively analyzed.In addition, The retrieval words " Combined oxidative phosphorylation deficiency 28, SLC25A26 gene" were used to search domestic and foreign databases.The clinical characteristics of combined phosphorylation deficiency 28 and the variation characteristics of SLC25A26 gene were summarized. Results:(1) A female patient full-term delivered after 30 min presented with groaning breath was admitted.Her main manifestations included pale complexion, groaning breathing, metabolic acidosis, and high lactate and pyruvate levels.Symptomatic support treatment like anti-infection and assisted ventilation were given, but her condition gradually worsened and died of respiratory and circulatory failure on the day of admission.The child was compound heterozygous mutation of SLC25A26 gene, the terminating mutation of exon 5 c. 403G>T caused the protein change to p. E135, and the non-synonymous mutation of exon 4 c. 212A>G caused the protein change to p. Y71C.(2) A total of 3 cases of COXPD-28 were searched in online databases, and no cases were reported in China.Through literature review, clinical features of COXPD-28 mainly included respiratory and circulatory fai-lure, elevations of lactate and pyruvate, and reductions of complexes Ⅰ, Ⅲ and Ⅳ in muscle biopsy.Two types of mutations in the SLC25A26 gene were detected, including 3 cases of missense mutations and 1 case of splicing mutation. Conclusions:COXPD-28 is an autosomal recessive genetic disease involving multiple systems and mitochondrial dysfunction.Mutations in the SLC25A26 gene is the pathological cause of COXPD-28.

13.
Article in Chinese | WPRIM | ID: wpr-930458

ABSTRACT

The clinical and genetic features of a child with immunodeficiency, centromeric instability, facial anomalies syndrome type 2(ICF2)admitted to pediatrics of the First Affiliated Hospital of Shandong First Medical University in June 2017 were retrospectively analyzed and the literature was reviewed.A 13-month-old female patient with flat nasal bridge and hypertelorism presented to the hospital for recurrent infection for 1 year.Laboratory tests showed humoral immune deficiency with immunoglobulin(Ig)G, IgA and IgM.Whole-exome sequencing revealed a de novo heterozygous frameshift mutation c. 1237_1247del and a de novo heterozygous nonsense mutation c. 460A>T of ZBTB24 gene.Through searching " ICF syndrome" " immunodeficiency, centromeric instability and facial anomalies syndrome" and " ZBTB24" in CNKI, Wanfang databases and PubMed published until August 2020, a total of 13 English language literatures involving 24 children with ICF2 were searched.The most common facial anomalies were hyper-telorism, epicanthus and flat nasal bridge.Most children had recurrent respiratory and digestive tract infections.All the children had humoral immune deficiency at varying degrees.All 24 children had ZBTB24 gene mutation, 16 mutations were reported, including 6 frameshift, 5 nonsense, 5 missense mutations.ICF syndrome is a rare autosomal recessive primary immunodeficiency with classic clinical manifestations, including humoral immune deficiency and facial anomalies.It can be diagnosed by genetic analysis.

14.
Article in Chinese | WPRIM | ID: wpr-930426

ABSTRACT

Objective:To report the second Chinese DeSanto-Shinawi syndrome (DESSH) case and to summarize the clinical characteristics and WAC gene mutation profiling in all published cases. Methods:A retrospective analysis was performed to evaluate the clinical characteristics and growth and development of a child with DESSH who had been regularly followed up in the Xiangyang No. 1 People′s Hospital, Hubei Medical College and Tianyou Hospital Affiliated to Wuhan University of Science and Technology.The relevant literature was reviewed to assess the relationship between clinical phenotype and spectrum of WAC gene mutation. Results:The female baby with DESSH was regularly evaluated for growth and development till the present age of 1 year and 3 months.She presented with growth and mental retardation, hypotonia, facial dysmophism and microcephaly.Whole-exome sequencing revealed a new de novo pathogenic mutation in the WAC gene (c.1090dupA, p.Arg364Lysfs*14) that has not been reported before.Analysis of 31 reported DESSH cases from 29 families showed that all of them had nonsense mutations or frame-shift mutations in WAC gene, which resulted in the loss of the coiled-coil region of WAC.Twenty-five cases (88.6%) were new mutations of WAC, and 6 cases (19.4%) were chimeric inheritance of gonad.Only 35.5% of them simultaneously lost both the WW domain in truncated WAC protein. Conclusions:DESSH is characterized by facial dysmophism, overall developmental delay and epileptic encephalopathy.This second Chinese DESSH baby was severe with an earlier onset and caused by a new mutation in WAC gene.All DESSH is caused by nonsense mutations or frameshift mutations of WAC gene resulting in the loss of coiled-coil region.There is no significant corresponding phenotype-genotype correlations in those DESSH cases.

15.
Article in Chinese | WPRIM | ID: wpr-930390

ABSTRACT

Objective:To explore the characteristics, clinical manifestations and gene mutation types of Cornelia de Lange syndrome (CdLs), and to improve the understanding of the disease.Methods:Clinical data and gene test results of a pediatric case of CdLs diagnosed in the First Affiliated Hospital of Xinxiang Medical University in August 2019 were analyzed retrospectively.Results:A female patient with 2 years and 8 months old presented a special appearance with a low and flat nose, a wide eye distance, audition ears, a downward inclination of the mouth corner, a high arch of the jaw and a small jaw deformity, who had recurrent seizures, speech and mental retardation.The result of gene test showed the mutation of SMC1A gene c. 2923C > T, and thus the patient was diagnosed as type 2 CdLs. Conclusions:CdLs is a rare genetic metabolic disease with special facial features and physical signs.There is only one case of CdLs with gene mutation of SMC1A in China through literature review.The mutation of SMC1A gene c. 2923C>T in CdLs cases has not been reported at home and abroad, which expands the variation spectrum of the SMC1A gene.

16.
Article in Chinese | WPRIM | ID: wpr-930386

ABSTRACT

Objective:To summarize the clinical and gene mutation characteristics of a child with developmental epileptic encephalopathy (DEE) caused by ubiquitin-like modifier-activating enzyme 5( UBA5 )gene mutation, and to perform literature review. Methods:Clinical characteristics and genetic test results of a case of DEE treated in Department of Neurology, Xuzhou Children′s Hospital, Xuzhou Medical University, in March 2020 were retrospectively analyzed.Relevant literatures reporting DEE cases caused by UBA5 gene mutations published before June 2020 were searched in the PubMed, CNKI, Wanfang and other online databases with the following key words: epilepsy encephalopathy, developmental encephalopathy, epileptic encephalopathy, Developmental encephalopathy and UBA5. Results:A female case with 7 months and 23 days old presented epileptic spasms at 4 months of age, and the condition was uncontrolled by medication of adrenocorticotropic hormone (ACTH) and several antiepileptic drugs.The patient later progressed to recurrent, treatment-resistant seizures with arrested development, short stature, microcephaly, expressionless face, irritability, unsteady head, lack of follow-up vision, lack of laughing, and limb hypotonia.Whole exome sequencing revealed a missense mutation and a microdeletion in the UBA5 gene, and the missense mutation was paternal c. 722A>C (p.E241A), located in the 8 th exon region.The microdeletion deletion was maternally derived from the 5 th to 11 th exon, which constituted a compound heterozygous mutation.A total of 5 foreign literatures involving 18 children with DEE and 0 domestic literatures were retrieved.Combined with the present case, all 19 cases presented refractory seizures in the early infancy, and most of them were epileptic spasms (63.2%, 12/19 cases), followed by myoclonus (31.6%, 6/19 cases). The birth history of all children was unremarkable, and they later presented developmental disabilities at varying degrees, mainly including microcephaly (94.7%, 18/19 cases), lack of follow-up vision (89.5%, 17/19 cases), and short stature (94.7%, 18/19 cases), intellectual disabilities (89.5%, 17/19 cases), movement disorders (84.2%, 16/19 cases) and hypotonia (100.0%), 13/19 cases (68.4%) died.EEG results mainly revealed normal or hypsarrhythmia, but 1 case presented suppression- burst.Brain magnetic resonance imaging (MRI) findings mainly included delayed myelination (47.4%, 9/19 cases), brain atrophy (52.6%, 10/19 cases), and thin corpus callosum (26.3%, 5/19 cases). Conclusions:Children with UBA5 gene mutations often have refractory seizures in the early infancy, which are mainly epileptic spasms.They also show severe psychomotor developmental delay, microcephaly and dystonia, with an extremely poor prognosis.Brain MRI suggested varying degrees of myelin dysplasia, brain trophy, and thin corpus callosum.For cases with the above clinical manifestations, genetic testing should be considered to confirm the diagnosis.

17.
Article in Chinese | WPRIM | ID: wpr-929808

ABSTRACT

Congenital cardiovascular disease is a kind of congenital disease caused by the interaction of multiple factors such as heredity, environment and pregnancy infection, but its exact etiology is still unclear.With the deepening of research, more and more evidences show that genetic factors play a significant role in its pathogenesis.Many genes are involved in the development of heart embryos, and the mutation of these genes often leads to congenital cardiovascular diseases.Homology modeling is a technique to predict the structural and functional changes of proteins caused by gene mutation through computer algorithm, and its application in the pathogenesis of congenital diseases has become a future trend.The purpose of this paper is to review homology modeling and its application in pathogenesis of congenital cardiovascular diseases briefly.

18.
Article in Chinese | WPRIM | ID: wpr-929800

ABSTRACT

Genetic factors are important causes of drug-resistant epilepsy.In most cases, epilepsy caused by gene mutation cannot be controlled by existing antiepileptic drugs.Ketogenic diet controls seizures through multi-target mechanism, which is widely used in the treatment of drug-resistant epilepsy caused by gene mutation.In this paper, the advance in application and efficacy of ketogenic diet therapy in 23 kinds of gene mutation related drug-resistant epilepsy is reviewed, which involves energy metabolism, ion channel, mTOR signaling pathway and some other rare diseases.

19.
Article in Chinese | WPRIM | ID: wpr-929732

ABSTRACT

Objective:To investigate the clinical characteristics, diagnosis and treatment methods of children with gene mutation-negative essential thrombocytosis (ET).Methods:The clinical data of a child with gene mutation-negative ET in the Blood Diseases Hospital of Chinese Academy of Medical Sciences were collected, and the related literature was reviewed.Results:The epistaxis was the main clinical symptom of this child. He was diagnosed as ET (gene mutation-negative) by bone marrow aspiration and gene detection. After hydroxyurea treatment, the platelet count increased and the clinical symptoms were improved.Conclusions:The incidence rate of ET in children is low, and the frequency of gene mutation-negative ET in children reported in the literature is different. The large number of samples and long-term follow-up studies are needed.

20.
Article in Chinese | WPRIM | ID: wpr-929726

ABSTRACT

Objective:To investigate the distribution characteristics of gene mutations and their relationship with prognosis in newly diagnosed patients with acute myeloid leukemia (AML).Methods:The clinical data of 225 newly diagnosed AML (non-acute promyelocytic leukemia) patients in the Second Affiliated Hospital (Tangdu Hospital) of Air Force Medical University from May 2016 to December 2019 were retrospectively analyzed. Thirty-four gene mutations related to AML, myelodyplastic syndrome (MDS) and myeloproliterative neoplasms (MPN) were detected by second-generation sequencing. The distribution of all gene mutations and its difference among different age groups were analyzed, and the differences in survival of patients with different gene mutations were compared. The Cox regression model was employed to analyze the survival influencing factors of patients aged <60 years old and ≥60 years old.Results:A total of 496 gene mutation sites were detected in 225 patients, with a median variant allel frequency (VAF) of 38.55% (1.00%-94.86%) and a median gene mutations of 3/case (0-8/case). The genes with high mutation frequency were ASXL1, CEBPA, NPM1, NRAS, FLT3-ITD, DNMT3A, IDH2, TET2, RUNX1, and IDH1. The gene mutation rates of TET2, SRSF2 and SF3B1 in patients aged ≥60 years old (56 cases) were higher than those in patients aged <60 years old (169 cases), and the differences were statistically significant (all P < 0.01). The proportion of patients aged ≥60 years old with 3 or more gene mutations was higher than that of patients aged <60 years old [53.6% (30/56) vs. 33.1% (56/169), χ2 = 7.44, P = 0.006]. The overall survival (OS) of patients with TP53, RUNX1 or FLT3-ITD gene mutation was worse than that of wild-type patients, the OS of patients with CEBPA double mutations was better than that of patients with CEBPA single mutation or wild-type, and the differences were statistically significant (all P < 0.05). Multivariate Cox regression analysis showed that CEBPA ( HR = 0.279, 95% CI 0.084-0.926, P = 0.037), TET2 ( HR = 2.611, 95% CI 1.115-6.111, P = 0.027) and TP53 ( HR = 3.609, 95% CI 1.159-11.234, P = 0.027) gene mutations were independent factors affecting the survival of AML patients aged <60 years old, ASXL1 ( HR = 3.523, 95% CI 1.385-8.962, P = 0.008), FLT3-ITD ( HR = 4.618, 95% CI 1.813-11.762, P = 0.001) and NRAS ( HR = 2.896, 95% CI 1.166-7.000, P = 0.022) were independent risk factors of the survival of AML patients aged ≥60 years old. Conclusions:There are differences in the distribution of gene mutations among AML patients with different age, and the elderly patients are more likely to have multiple gene mutations at the same time. In addition to the currently known CEBPA double mutations, TP53, ASXL1, RUNX1 and other gene mutations, TET2 and NRAS gene mutations may also be factors affecting the prognosis.

SELECTION OF CITATIONS
SEARCH DETAIL