scholarly journals Clinical manifestations and phenotypic analysis of new ANK1 gene mutations in 12 Chinese children with hereditary spherocytosis

2019 ◽  
Author(s):  
Fei Xie ◽  
Lei Lei ◽  
Bin Cai ◽  
Lu Gan ◽  
Yu Gao ◽  
...  
Keyword(s):  
Structural Changes ◽  
Second Generation ◽  
Hereditary Spherocytosis ◽  
Effective Means ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Chinese Children ◽  
Coding Region ◽  
Sequencing Technology ◽  
Genome Database

AbstractObjectiveTo summarize the clinical features and laboratory examination of ANK1 gene in 12 children with hereditary spherocytosis in China, and to determine the genetic mutations in those children.MethodsThe clinical data of children and their parents were collected and analyzed. The sequence of related genes was analyzed by second-generation sequencing technology. The suspected pathogenic mutations were detected by Sanger sequencingResultsNew mutations in the coding region of ANK1 was detected in 12 patients, which caused amino acid changes in the gene encoding, causing structural changes or loss of function.ConclusionANK1 (c.1914_c.1918delTTTG), ANK1 (c.399T>G), ANK1 (c.1564delC), ANK1 (c.4439dupA<br>), ANK1 (c.4510_4513del), ANK1 (c.2961delC), ANK1 (c.2142dupT), ANK1 (c.2858+1G>C), ANK1 (c.3235delG), ANK1 (c.4739A>G), ANK1 (c.2638-2 A>G), ANK1 (c. 4739A>G) mutations in the coding region of the gene are the cause of suspicious disease in these 12 Chinese children. At the same time, second-generation gene sequencing technology is an effective means of confirming HS. Different types of mutations (P=0.388)and different mutation areas (P=0.660)had no significant effect on the severity of anemia. The 12 gene mutation sites in this study have not been included in the human genome database, dbSNP (v138) and ExAC databases. The new ANK1 gene mutations found in HS children can provide further exploration of the genetic etiology of HS in Chinese population.

scholarly journals Analysis on the pathogenic genes of 60 Chinese children with congenital hyperinsulinemia

2018 ◽  
Vol 7 (12) ◽  
pp. 1251-1261
Author(s):  
Zi-Di Xu ◽  
Wei Zhang ◽  
Min Liu ◽  
Huan-Min Wang ◽  
Pei-Pei Hui ◽  
...  
Keyword(s):  
Clinical Manifestations ◽  
Gene Mutations ◽  
Chinese Children ◽  
Treatment Modalities ◽  
Partial Pancreatectomy ◽  
Genetic Characteristics ◽  
Pathogenic Genes ◽  
Second Generation Sequencing ◽  
Long Term Prognosis

This study aims to summarize and analyze the clinical manifestations, genetic characteristics, treatment modalities and long-term prognosis of congenital hyperinsulinemia (CHI) in Chinese children. Sixty children with CHI, who were treated at Beijing Children’s Hospital from January 2014 to August 2017, and their families, were selected as subjects. The CHI-related causative genes in children were sequenced and analyzed using second-generation sequencing technology. Furthermore, the genetic pathogenesis and clinical characteristics of Chinese children with CHI were explored. Among the 60 CHI children, 27 children (27/60, 45%) carried known CHI-related gene mutations: 16 children (26.7%) carried ABCC8 gene mutations, seven children (11.7%) carried GLUD1 gene mutations, one child carried GCK gene mutations, two children carried HNF4α gene mutations and one child carried HADH gene mutations. In these 60 patients, eight patients underwent 18F-L-DOPA PET scan for the pancreas, and five children were found to be focal type. The treatment of diazoxide was ineffective in these five patients, and hypoglycemia could be controlled after receiving partial pancreatectomy. In conclusion, ABCC8 gene mutation is the most common cause of CHI in Chinese children. The early genetic analysis of children’s families has an important guiding significance for treatment planning and prognosis assessment.

HISTOLOGICAL CHANGES IN THE INTESTINES OF POULTRY DURING FODDER INTOXICATION

2020 ◽  
Author(s):  
E.P. Dolgov ◽  
◽  
A.A. Abramov ◽  
E.V. Kuzminova ◽  
E.V. Rogaleva ◽  
...  
Keyword(s):  
Body Weight ◽  
Histological Examination ◽  
Aflatoxin B1 ◽  
Structural Changes ◽  
Clinical Manifestations ◽  
Feed Additives ◽  
The Body ◽  
Histological Changes ◽  
Beet Pulp

The article presents the data on the study of the influence of mycotoxins combination (T-2 toxin at the concentration of 0.095 mg/kg and aflatoxin B1 in the concentration of 0.019 mg/kg) on the body of quails and the results of pharmacocorrection of toxicosis with a complex consisting of beet pulp and lecithin. Structural changes in the intestines of quais at fodder mycotoxicosis are described. The use of antitoxic feed additives in poultry led to a weakening of the action of xenobiotics, which was confirmed by an increase in the safety of poultry and increase in body weight of quails, a decrease in the clinical manifestations of intoxication, as well as in positive changes in the structure of the intestine of the poultry during histological examination.

scholarly journals Novel missense mutation of SASH1 in a Chinese family with dyschromatosis universalis hereditaria

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Lu Cao ◽  
Ruixue Zhang ◽  
Liang Yong ◽  
Shirui Chen ◽  
Hui Zhang ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Sequence Alignment ◽  
Multiple Sequence Alignment ◽  
Molecular Genetic ◽  
Family Members ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Mendelian Inheritance ◽  
Chinese Family ◽  
Multiple Sequence

Abstract Background Dyschromatosis universalis hereditaria (DUH) is a pigmentary dermatosis characterized by generalized mottled macules with hypopigmention and hyperpigmention. ABCB6 and SASH1 are recently reported pathogenic genes related to DUH, and the aim of this study was to identify the causative mutations in a Chinese family with DUH. Methods Sanger sequencing was performed to investigate the clinical manifestation and molecular genetic basis of these familial cases of DUH, bioinformatics tools and multiple sequence alignment were used to analyse the pathogenicity of mutations. Results A novel missense mutation, c.1529G>A, in the SASH1 gene was identified, and this mutation was not found in the National Center for Biotechnology Information Database of Short Genetic Variation, Online Mendelian Inheritance in Man, ClinVar, or 1000 Genomes Project databases. All in silico predictors suggested that the observed substitution mutation was deleterious. Furthermore, multiple sequence alignment of SASH1 revealed that the p.S510N mutation was highly conserved during evolution. In addition, we reviewed the previously reported DUH-related gene mutations in SASH1 and ABCB6. Conclusion Although the affected family members had identical mutations, differences in the clinical manifestations of these family members were observed, which reveals the complexity of the phenotype-influencing factors in DUH. Our findings reveal the mutation responsible for DUH in this family and broaden the mutational spectrum of the SASH1 gene.

scholarly journals Prevalence and clinical phenotype of the triplicated α-globin genes and its ethnic and geographical distribution in Guizhou of China

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Xi Luo ◽  
Xiang-mei Zhang ◽  
Liu-song Wu ◽  
Jindong Chen ◽  
Yan Chen
Keyword(s):  
Genetic Counseling ◽  
Peripheral Blood ◽  
Clinical Phenotype ◽  
Globin Gene ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Guizhou Province ◽  
Globin Genes ◽  
Phenotype Correlation ◽  
Chi Square

Abstract Background α-thalassemia is relatively endemic in Guizhou province of southwestern China. To predict the clinical manifestations of α-globin gene aberration for genetic counseling, we examined the prevalence of the α-globin triplication and the genotype–phenotype correlation in this subpopulation Methods A cohort of 7644 subjects was selected from nine ethnicities covering four regions in Guizhou province of China. Peripheral blood was collected from each participant for routine blood testing and hemoglobin electrophoresis. PCR-DNA sequencing and Gap-PCR were used to identify the thalassemia gene mutations. Chi-square tests and one-way analysis of variance (ANOVA) were used to statistically analyze the data. Results We found that the frequency of α-globin triplication in Guizhou province was 0.772% (59/7644). Genotypically, the αααanti4.2/αα accounted for 0.523% (40/7644), the αααanti3.7/αα for 0.235% (18/7644), and the αααanti3.7/–SEA for 0.013% (1/7644). The αααanti4.2/αα is more prevalent than the αααanti3.7/αα in Guizhou. In addition, the frequency of the HKαα/αα (that by GAP-PCR is like αααanti4.2/-α3.7) was 0.235% (18/7644). Ethnically, the Tujia group presented the highest prevalence (2.47%) of α-globin triplication. Geographically, the highest frequency of the α-globin triplication was identified in Qiannan region (2.23%). Of the triplicated α-globin cases, 5 coinherited with heterozygote β-thalassemia and presented various clinical manifestations of anemia. Conclusions These data will be used to update the Chinese triplicated α-globin thalassemia database and provide insights into the pathogenesis of thalassemia. These findings will be helpful for the diagnosis of thalassemia and future genetic counseling in those regions.

Evaluation of the tshr gene reveals polymorphisms associated with typical symptoms in primary congenital hypothyroidism

2016 ◽  
Vol 29 (1) ◽  
Author(s):  
Erik Artur Cortinhas Alves ◽  
Raissa Coelho Andrade ◽  
Carlos Eduardo de Melo Amaral ◽  
Milena Coelho Fernandes Caldato ◽  
Adriana Maria Rocha Bastos ◽  
...  
Keyword(s):  
Congenital Hypothyroidism ◽  
Peripheral Blood ◽  
Genomic Dna ◽  
Gene Mutations ◽  
Molecular Heterogeneity ◽  
Coding Region ◽  
Blood Samples ◽  
Live Births ◽  
Tshr Gene ◽  
Inactivating Mutations

AbstractPrimary congenital hypothyroidism (PCH) has an incidence of approximately 1 in each 3000–4000 live births. In the last two decades, nearly 50 types of the distinct inactivating mutations have already been described in the coding region of the tshr gene. The aim of present study was to investigate tshr gene mutations in patients with primary congenital hypothyroidism, analyzing a sample of 106 patients that were diagnosed with PCH. Genomic DNA was isolated from peripheral blood samples, and 10 exons from the TSH receptor were automatically sequenced. Five nucleotide alterations (P52T, N187N, A459A, L645L, and D727E. N187N and D727E polymorphisms) were associated with positive medical history. In view of the clinical, biochemical and molecular heterogeneity of the etiology of the PCH, the study of polymorphisms is critical for investigating the possible associations with prevailing symptoms of this disorder.

Clinical Characteristics and Genetic Analysis of Interstitial Lung Disease in Chinese Children (Genes and Interstitial Lung Disease)

2021 ◽  
Author(s):  
Mei-Xia Huang ◽  
Lu Qin ◽  
Fei-Zhou Zhang ◽  
Lei Wu ◽  
Jia-Hui Yu ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Clinical Characteristics ◽  
Clinical Manifestations ◽  
Failure To Thrive ◽  
Surfactant Protein ◽  
Chinese Children ◽  
Common Mutation ◽  
Onset Age ◽  
Surfactant Dysfunction

Abstract BackgroundMutation in the surfactant protein C gene (SFTPC) is a cause of interstitial lung disease (ILD). Our objective was to investigate the clinical characteristics, outcome and influencing factors of ILD in Chinese children with SFTPC mutations.MethodA total of 8 Chinese children with ILD heterozygous for SFTPC mutations that were treated in our hospital from January 2014 to December 2020 were included in our study. Candidate genes responsible for surfactant dysfunction were sequenced by next-generation sequencing. The clinical and genetic data were reviewed retrospectively.ResultsThe children’s onset age was before the age of 2 years, and one case was just after birth. The most significant clinical manifestations were cough, tachypnea, hypoxemia and failure to thrive. The most common mutation was p. lle73Thr, which accounted for 87.5% (7/8) of our patients. Four patients whose onset was within 3 months, including 3 children with CMV infection, died. Conclusionp. lle73Thr mutation of SFTPC was an important and common cause of ILD in the Chinese children. The clinical manifestations of ILD associated with this mutation are not specific. The severity and outcome of the disease may be affected by factors such as onset age and viral infection.

Three novel mutations of the BCKDHA, BCKDHB and DBT genes in Chinese children with maple syrup urine disease

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Jianmei Yang ◽  
Jianjun Xiu ◽  
Yan Sun ◽  
Fan Liu ◽  
Xiaohong Shang ◽  
...  
Keyword(s):  
Maple Syrup Urine Disease ◽  
Structural Changes ◽  
Clinical Manifestations ◽  
Autosomal Recessive Disorder ◽  
Novel Mutations ◽  
Metabolic Encephalopathy ◽  
Maple Syrup ◽  
Feeding Difficulties ◽  
Urine Disease ◽  
The Impact

Abstract Background Maple syrup urine disease (MSUD) is a rare metabolic autosomal recessive disorder caused by deficiency of the branched-chain α-ketoacid dehydrogenase complex. Mutations in the BCKDHA, BCKDHB and DBT genes are responsible for MSUD. This study presents the clinical and molecular characterizations of four MSUD patients. Methods Clinical data of patients were retrospectively analyzed, and genetic mutations were identified by whole-exome sequencing. CLUSTALX was employed to analyzed cross-species conservation of the mutant amino acid. The impact of the mutations was analyzed with PolyPhen-2 software. The I-TASSER website and PyMOL software were used to predict the protein three-position structure of the novel mutations carried by the patients. Results Vomiting, irritability, feeding difficulties, seizures, dyspnoea, lethargy and coma were the main clinical presentations of MSUD. Cranial MRI showed abnormal symmetrical signals in accordance with the presentation of inherited metabolic encephalopathy. Seven mutations were detected in four patients, including three novel pathogenic mutations in the BCKDHA (c.656C>A), BCKDHB (deletion of a single-copy of BCKDHB) and DBT (c.1219dup) genes. Structural changes were compatible with the observed phenotypes. Conclusions Different types of MSUD can display heterogeneous clinical manifestations. Exhaustive molecular studies are necessary for a proper differential diagnosis. The newly identified mutation will play a key role in the prenatal diagnosis of MSUD in the future.

IDENTIFICATION, SEQUENCE AND EXPRESSION OF A CRUSTACEAN CARDIOACTIVE PEPTIDE (CCAP) GENE IN THE MOTHMANDUCA SEXTA

2001 ◽  
Vol 204 (16) ◽  
pp. 2803-2816 ◽  
Author(s):  
P. K. LOI ◽  
S. A. EMMAL ◽  
Y. PARK ◽  
N. J. TUBLITZ
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Gene Structure ◽  
Expression Patterns ◽  
Amino Acid Residues ◽  
Coding Region ◽  
Genome Database ◽  
Reading Frame ◽  
Crustacean Cardioactive Peptide ◽  
Embryonic Life

SUMMARYThe crustacean cardioactive peptide (CCAP) gene was isolated from the tobacco hawkmoth Manduca sexta. The gene has an open reading frame of 125 amino acid residues containing a single, complete copy of CCAP. Analysis of the gene structure revealed three introns interrupting the coding region. A comparison of the M. sexta CCAP gene with the Drosophila melanogaster genome database reveals significant similarities in sequence and gene structure.The spatial and temporal expression patterns of the CCAP gene in the M. sexta central nervous system were determined in all major post-embryonic stages using in situ hybridization techniques. The CCAP gene is expressed in a total of 116 neurons in the post-embryonic M. sextacentral nervous system. Nine pairs of cells are observed in the brain, 4.5 pairs in the subesophageal ganglion, three pairs in each thoracic ganglion(T1-T3), three pairs in the first abdominal ganglion (A1), five pairs each in the second to sixth abdominal ganglia (A2-A6) and 7.5 pairs in the terminal ganglion. The CCAP gene is expressed in every ganglion in each post-embryonic stage, except in the thoracic ganglia of first- and second-instar larvae. The number of cells expressing the CCAP gene varies during post-embryonic life,starting at 52 cells in the first instar and reaching a maximum of 116 shortly after pupation. One set of thoracic neurons expressing CCAP mRNA shows unusual variability in expression levels immediately prior to larval ecdysis. Using previously published CCAP immunocytochemical data, it was determined that 91 of 95 CCAP-immunopositive neurons in the M. sexta central nervous system also express the M. sexta CCAP gene, indicating that there is likely to be only a single CCAP gene in M. sexta.

scholarly journals Clinical manifestations of familial exudative vitreoretinopathy in children with nucleotide sequence alterations in the FZD4 gene

2021 ◽  
Vol 14 (4) ◽  
pp. 52-59
Author(s):  
L. A. Katargina ◽  
V. V. Kadyshev ◽  
E. V. Denisova ◽  
E. A. Geraskina ◽  
A. V. Marakhonov ◽  
...  
Keyword(s):  
Nucleotide Sequence ◽  
Direct Sequencing ◽  
Molecular Genetic ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Interdisciplinary Approach ◽  
Ophthalmological Examination ◽  
Photographic Recording ◽  
Familial Exudative Vitreoretinopathy ◽  
National Medical

Familial exudative vitreoretinopathy (FEVR)is a rare genetically heterogeneous disease with multiple types of inheritance (autosomal dominant, autosomal recessive, X-linked) and widely varying clinical features. Up to 40 % of cases of FEVR are associated with mutations of the FZD4 gene.Purpose: to investigate the clinical manifestations of FEVR in children with nucleotide sequence alterations in the FZD4 gene. Material and methods. The Helmholtz National Medical ResearchCenter of Eye Diseases and the ResearchCentre for MedicalGenetics conducted a joint in-depth ophthalmological examination of 18 patients aged from 3 weeks to 17 years with a diagnosis of FEVR, which included a detailed ophthalmoscopy under drug mydriasis, ultrasound and electrophysiological examination, photographic recording of fundus changes using RetCam and Fundus Foto. Molecular genetic examination was carried out by direct sequencing according to Sanger. Results. Nucleotide sequence alterations in the FZD4 gene were detected in 3 patients(16.7 %)from two unrelated families. In one family, a 12-year-old girl wasfound to display the firstsymptoms of ophthalmic pathology (reduced vision, strabismus) at the age of 3.5 years. In another family, the clinical manifestations of FZD4 gene mutations were observed in two children during the first year of life (at the age of 5 and 11 months).Conclusions. The clinical picture of 3 patients with detected changes in the nucleotide sequence of the FZD4 gene is characterized by early manifestation and bilateral asymmetric ophthalmoscopic damage. The results of the study indicate the need for a timely diagnosis of FEVR in young children, recommend an interdisciplinary approach to the study of the disease, which should contribute to a better understanding of pathogenesis, and the development of an effective diagnostic, treatment and rehabilitation algorithm.

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