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.

scholarly journals FBN1 gene mutations in patients with congenital ectopia lentis caused by Marfan syndrome

2020 ◽  
Vol 17 (1) ◽  
pp. 87-100
Author(s):  
A. A. Gusina ◽  
N. S. Stalybko ◽  
K. A. Krinitskaya ◽  
V. F. Ivanova ◽  
N. V. Rumiantseva ◽  
...  
Keyword(s):  
Direct Sequencing ◽  
Molecular Genetic ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Heterozygous State ◽  
Genetic Studies ◽  
Ectopia Lentis ◽  
Fbn1 Gene ◽  
Common Causes ◽  
Families With Children

The prevalence of congenital ectopia lentis is 7–10 cases per 100 000 people. The most common causes of congenital lens displacement are the FBN1 gene mutations that have been found in 25–85 % of patients with this pathology. The aim of the study is to establish the FBN1 gene mutations in patients with congenital lens displacement and in their families. The study group included three families with children and adults suffered from the congenital lens dislocation. The nucleotide sequence of the FBN1 gene was analyzed by direct sequencing. The pathogenicity of the identified mutations was assessed using the Ghent criteria revised in 2010. The mutation c.1884C> G (p.Cys628Trp) in the heterozygous state in the 16th exon of the FBN1 gene was detected in proband 1 and her brother. Proband 2 was found to be a heterozygous career of the mutation c.2461T> A (p.Cys821Ser) in the 21st exon; this mutation was absent in parents and a healthy brother. The mutation c.7851delС (p.Cys2617Trpfs*65) in the heterozygous state in the 64th exon was identified in proband 3 and her mother. In accordance with the revised Ghent classification and the clinical manifestations and molecular genetic studies, Marfan’s syndrome (MS) was diagnosed in all probands and their affected relatives. We detected three pathogenic mutations not previously described in the literature in the 16th, 21st, and 64th exons of the FBN1 gene in patients with congenital ectopia lentis caused by MS. We established the spectrum of clinical manifestations of MS characteristic for the identified mutations.

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 Novel Norrie disease gene mutations in Chinese patients with familial exudative vitreoretinopathy

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Li-Yun Jia ◽  
Kai Ma
Keyword(s):  
Disease Gene ◽  
Direct Sequencing ◽  
Venous Blood ◽  
Gene Mutations ◽  
Chinese Patients ◽  
Control Group ◽  
Coding Region ◽  
Exon 2 ◽  
Norrie Disease ◽  
Familial Exudative Vitreoretinopathy

Abstract Purpose This study aims to analyze the Norrie disease gene (NDP) variants in patients with familial exudative vitreoretinopathy (FEVR) and their clinical features. Methods Thirty-three Chinese patients (22 familial and 11 simplex) who were diagnosed as FEVR underwent detailed ocular examinations in Beijing Tongren Hospital. Peripheral venous blood was drawn from the patients and their family members for the extraction of genomic DNA. All exons of NDP gene were analyzed by direct sequencing of PCR-amplified DNA fragments. Results Four novel mutations in NDP gene were identified in four X-linked FEVR families: a C → T transversion, c. 625C → T, in exon 3, resulting in a serine-to-proline change in codon 73 (S73P); a C → G transition, c. 751C → G, in exon 3, resulting in an arginine-to-glycine change in codon 115 (R115G); a T → C transversion of nucleotide 331 at 5’UTR in exon 2 (c.331 T → C); and a C → T transversion of the nucleotide 5 in intron 1 (IVS1 + 5C → T). The mutations were not present in the control group (n = 100). Conclusions Our results extend the spectrum of NDP gene mutations. The mutations in the non-coding region of NDP may play a crucial role in the pathogenesis of FEVR.

Glomerulocystic Kidney: One Hundred–Year Perspective

2010 ◽  
Vol 134 (4) ◽  
pp. 583-605 ◽  
Author(s):  
Jochen K. Lennerz ◽  
David C. Spence ◽  
Samy S. Iskandar ◽  
Louis P. Dehner ◽  
Helen Liapis
Keyword(s):  
In Silico ◽  
Molecular Genetic ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
In Silico Analysis ◽  
Gene Encoding ◽  
Cystic Kidneys ◽  
Proposed Model ◽  
Glomerular Cysts ◽  
Glomerulocystic Kidney

Abstract Context.—Glomerular cysts, defined as Bowman space dilatation greater than 2 to 3 times normal size, are found in disorders of diverse etiology and with a spectrum of clinical manifestations. The term glomerulocystic kidney (GCK) refers to a kidney with greater than 5% cystic glomeruli. Although usually a disease of the young, GCK also occurs in adults. Objective.—To assess the recent molecular genetics of GCK, review our files, revisit the literature, and perform in silico experiments. Data Sources.—We retrieved 20 cases from our files and identified more than 230 cases published in the literature under several designations. Conclusions.—Although GCK is at least in part a variant of autosomal dominant or recessive polycystic kidney disease (PKD), linkage analysis has excluded PKD-associated gene mutations in many cases of GCK. A subtype of familial GCK, presenting with cystic kidneys, hyperuricemia, and isosthenuria is due to uromodullin mutations. In addition, the familial hypoplastic variant of GCK that is associated with diabetes is caused by mutations in TCF2, the gene encoding hepatocyte nuclear factor–1β. The term GCK disease (GCKD) should be reserved for the latter molecularly recognized/inherited subtypes of GCK (not to include PKD). Review of our cases, the literature, and our in silico analysis of the overlapping genetic entities integrates established molecular-genetic functions into a proposed model of glomerulocystogenesis; a classification scheme emerged that (1) emphasizes the clinical significance of glomerular cysts, (2) provides a pertinent differential diagnosis, and (3) suggests screening for probable mutations.

scholarly journals Variant of the FLNC gene nucleotide sequence in a family with different phenotypic manifestations of left ventricular non-compaction

2021 ◽  
Vol 26 (10) ◽  
pp. 4748
Author(s):  
O. V. Kulikova ◽  
R. P. Myasnikov ◽  
A. N. Meshkov ◽  
M. M. Kudryavtseva ◽  
E. A. Mershina ◽  
...  
Keyword(s):  
Case Report ◽  
Nucleotide Sequence ◽  
Scientific Literature ◽  
Molecular Genetic ◽  
Clinical Manifestations ◽  
Left Ventricular ◽  
Gene Variants ◽  
Molecular Genetic Testing ◽  
Gene Nucleotide Sequence ◽  
I Gene

Left ventricular non-compaction is a heterogeneous heart disease with various phenotypic and clinical manifestations. The article presents the results of clinical, instrumental and molecular genetic investigations of a family with diagnosed left ventricular non-compaction (LVNC) with different clinical and phenotypic manifestations. As a result of a molecular genetic testing, all family members with the LVNC phenotype were found to have a likely pathogenic variant in the FLNC gene. Variants in this gene are associated with a number of cardiomyopathies: dilated, hypertrophic, and restrictive. In the international scientific literature, isolated clinical cases of LVNC development with variants of the FLNC gene nucleotide sequence are presented. In our work, we present a case report of LVNC with a variety of clinical manifestations within the same family.

Combined Congenital Hypodysfibrinogemia and Factor XI Deficiency in a Chinese Family

2020 ◽  
Vol 143 (5) ◽  
pp. 472-477
Author(s):  
Yan Peng ◽  
Longjian Nie ◽  
Cong Qin ◽  
Lagen Wan ◽  
Puhui Zhou
Keyword(s):  
Direct Sequencing ◽  
Molecular Genetic ◽  
Gene Mutations ◽  
Chinese Family ◽  
Bleeding Tendency ◽  
Missense Mutations ◽  
Factor Xi ◽  
Mutation Site ◽  
Fibrin Polymerization ◽  
Factor Xi Deficiency

Both congenital hypodysfibrinogenemia and factor XI deficiency are rare coagulopathies caused by mutations within the fibrinogen and F11 genes, respectively. To investigate the pathogenesis of combined congenital hypodysfibrinogenemia with factor XI (FXI) deficiency in a Chinese family, coagulation assays, FXI activity (the 1-stage method), fibrinogen activity (the Clauss method), and antigen (prothrombin time [PT]-derived method) were performed. The sequences of fibrinogen genes and F11 were amplified by PCR and analyzed by direct sequencing. The proband as well as his grandmother, father, aunt, and sister showed a low plasma concentration of fibrinogen measured by the Clauss method and a slightly decreased result by the PT-derived method; finally, c.1097A>G in exon 8 of FGG was detected in the pedigree, which caused His340Arg mutation. His grandfather had a slightly prolonged activated partial thromboplastin time (APTT) due to low FXI activity. FXI deficiency was a compound heterozygote inherited with missense mutations of c.434A>G in exon 5 as well as c.1253G>T in exon 11 which caused HGV p.His145Arg and Gly400Val mutations, respectively. The grandfather had no qualitative or quantitative defect in fibrinogen. The proband and his father and aunt had c.434A>G at the exon 5 mutation site and no decrease in FXI activity. His mother had no fibrinogen or F11 gene mutations. Plasma fibrin polymerization was delayed. The proband in our study showed typical changes of congenital hypodysfibrinogemia in the clotting analyses with delayed fibrin polymerization, but although he was a heterozygous carrier of the c.434A>G variant in the F11 gene, he had no decrease in FXI activity and no bleeding tendency, thus questioning the pathogenicity of the identified variant in the F11 gene. To our knowledge, this is the first report of a case of combined hypodysfibrinogenemia and FXI deficiency confirmed by molecular genetic tests.

scholarly journals Clinicopathological and Molecular Genomic Features of Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma in The Chinese Population: A Study of 20 Cases

2021 ◽  
Author(s):  
Chunni Chen ◽  
Yuxi Gong ◽  
Yefan Yang ◽  
Qiuyuan Xia ◽  
Qiu Rao ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Cells ◽  
Chinese Population ◽  
Cell Lymphoma ◽  
Molecular Genetic ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
T Cell Lymphoma ◽  
Molecular Features ◽  
Stat Pathway

Abstract Background Monomorphic epitheliotropic T-cell lymphoma (MEITL) is an aggressive non-Hodgkin lymphoma with a high fatality rate. This study was aimed to explore the clinicopathological and molecular genetic features of MEITL in the Chinese population. Methods A retrospective analysis was performed based on the clinical manifestations and pathological features of 20 Chinese MEITL. 9 cases with paired diseased-normal tissues were also analyzed for molecular information by whole-genome sequencing. Results There were 14 men and 6 women with a median age of 62.5 (28–81) years. 17(17/20) lesions were located in the jejunum or ileum; 13(13/20) cases had ulcers or perforations. Microscopically, except for 1(1/20) case of pleomorphic cells, the monomorphic, middle-sized tumor cells infiltrating into the intestinal epithelial and peripheral intestinal mucosa recess could be seen in the other 19 cases. Immunohistochemistry showed that most of the tumor cells in MEITL were positive for CD3(20/20), CD8(17/20), CD43(19/20), and CD56(15/20), but negative for CD5(20/20). The most frequently mutated genes of these Chinese cases were STAT5B (4/9) and TP53 (4/9), not SETD2(2/9). ZDBF2 mutations (4/9) were also detected for the first time with a high mutated frequency. We demonstrated that mutations of JAK-STAT pathway-related genes and the amplification of Chromosome 9q appeared at the same time in most cases(5/9). Conclusions The clinicopathological features were consistent with that in previous western studies, but a novel mutated gene, ZDBF2, was found in this study. A combination of gene mutations involved in the JAK-STAT pathway and the amplification of Chr9q may be used as one of the molecular features of MEITL diagnosis, especially when morphological and immunohistochemical evidence is insufficient.

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.

Molecular Epidemiological Monitoring of Circulation of Coxsackievirus A10

2021 ◽  
pp. 43-49
Author(s):  
LN Golitsyna ◽  
VV Zverev ◽  
NV Ponomareva ◽  
NI Romanenkova ◽  
Thao Thanh Thi Nguyen ◽  
...  
Keyword(s):  
Russian Federation ◽  
Molecular Genetic ◽  
Clinical Manifestations ◽  
Foot And Mouth Disease ◽  
Sewage Water ◽  
Epidemiological Surveillance ◽  
Molecular Monitoring ◽  
South Vietnam ◽  
Epidemiological Monitoring ◽  
The Russian Federation

Background: Coxsackievirus A10 (CV-A10) is currently one of the most common etiological agents of enterovirus infection (EVI). Over the past decade, severe and fatal cases of CV-A10 infection have become more frequent while clinical manifestations of the disease are similar to those of Enterovirus A71 infection. The objective of our study was to characterize circulation of Coxsackievirus A10 in the Russian Federation in 2008–2019 and to study the phylogenetic relationships of strains isolated in Russia and Vietnam. Materials and methods: In 2008–2019, 220 CV-A10 strains were isolated from patients with various clinical manifestations of EVI and from sewage water samples taken in the Russian Federation and then studied using molecular genetic methods. In addition to that, we analyzed 26 CV-A10 strains isolated from patients with hand, foot, and mouth disease (HFMD) and acute flaccid paralysis in South Vietnam in 2018–2019. Results: We established a two-year periodicity of CV-A10 active circulation in Russia. In the structure of clinical forms of CV-A10 infection, herpetic angina prevailed (30.8 %), followed by minor illness (25.25 %), respiratory diseases (15.66 %), exanthema (14.65 %), gastrointestinal disorders (8.08 %), and asymptomatic infections (2.02 %). Symptoms of CNS damage (meningitis, meningoencephalitis) were observed in 3.53 % of cases. Most CV-A10 strains from Vietnam were isolated from patients with CNS affection of varying degrees of severity. During the study period, CV-A10 strains of genotypes C, E, and F3 circulated in the territory of the Russian Federation whereas the strains from South Vietnam were represented by genotypes F3 and F1. The studied strains showed a genetic relationship with those of CV-A10 circulating in different countries. Vietnamese and some Russian strains of the F3 genotype were genetically close to the strains isolated from severe cases. Conclusions: Molecular monitoring of CV-A10 circulation is an important component of the global epidemiological surveillance of EVI.

MOLECULAR GENETIC CHARACTERISTICS OF COMPONENTS OF THE COMPLEMENT SYSTEM IN SEVERE ACNE

2021 ◽  
Vol 100 (2) ◽  
pp. 40-48
Author(s):  
A.G. Rumyantsev ◽  
◽  
A.G. Rumyantsev ◽  
O.M. Demina ◽  
◽  
...  
Keyword(s):  
Nucleotide Sequence ◽  
Complement System ◽  
Molecular Genetic ◽  
Factor H ◽  
Host Cells ◽  
Pathophysiological Mechanism ◽  
Genetic Characteristics ◽  
Severe Acne ◽  
C3 Gene ◽  
The Complement System

It has been shown that the inflammatory response in acne develops at the early subclinical stages of the disease, sometimes before the formation of comedones. It is known that an important component of the innate immune system is the complement system, which includes more than 60 components, including 9 basic proteins (C1-C9), a variety of activation products (C3a, C3b, iC3b, C3d and C3dg), regulatory and inhibitory molecules [factor H, fH-like protein 1 (FHL1), CR1 (CD35), C4b-binding protein (C4BP), C1inh and vitronectin], proteases and secreted enzymes (factor B, factor D, C3bBb and C4bC2b), as well as receptors for effector molecules [C3aR, C5aR, C5L2 and C1q receptor (C1qR)]. The compliment is the central part of innate immunity, which is the first line of protection against alien and altered host cells. The objectives of this study were to determine and analyze the variants of the nucleotide sequence of the genes of the complement system C1QA, C1S, C2, C3, C5, C6, C7, C8A, C8B, C8G, C9 in patients with severe acne. Materials and methods of research: To achieve the target a prospective open non-randomized one-center study was carried out in 2017–2020. Under our supervision in the clinical setting at the Department of Skin Diseases and Cosmetology of the Pirogov Russian National Research Medical University, there were 50 patients in the main group and 20 participants in the comparison group (70 people in total) (42/60% men and 28/40% women) aged 15 to 46 years (median – 22,1 years). Molecular genetic diagnostics was performed in all 70 patients of the main and control groups by the method of high-throughput DNA sequencing – next-generation sequencing (NGS). Results: when analyzing the nucleotide sequence variants of the complement system genes identified in our study, it is shown that the severe form of acne probably has an association (4 SNPs of the C8A gene, 1 SNPs of the C8B gene, 2 SNPs of the C1S gene, 3 SNPs of the C3 gene, 2 SNPs of the C9 gene, 1 SNPs of the C7 gene, 1 SNPs of the C6 gene, 1 SNPs of the C2 gene, 2 SNPs of the C5 gene, 2 SNPs of the C8G gene), 13 SNPs of the complement system genes in introns (1 SNPs of the C8A gene, 1 SNPs of the C8B gene, 2 SNPs of the C1S gene, 1 SNPs of the C3 gene, 1 SNPs of the C7 gene, 2 SNPs of the C6 gene, 4 SNPs of the C5 gene, 1 SNPs of C8G gene), 6 SNPs of the complement system genes (2 SNPs of the C8B gene: one SNPs each in the 3'UTR and 5'UTR zones; 3 SNPs of the C3 gene in the 5'UTR zone, 1 SNPs of the C7 gene in the 3'UTR zone). Two mutations of the frame shift of the C2 gene (frameshift deletion) and the C9 gene (rs748464075, frameshift insertion) seem to have a protective effect in the development of acne. Conclusion: the obtained variants of the nucleotide sequence of the genes of the complement system C1QA, C1S, C2, C3, C5, C6, C7, C8A, C8B, C8G, C9, apparently, are associated with the formation of severe acne and cause an imbalance of the components of the complement system. It can cause a defect in chemotactic and phagocytic reactions, and as a result a disturbance of the regulation of the inflammatory reaction with chronization of the skin process occures. Thus, results of studies carried out, revealed – for the first time – polymorphic loci of genes of components of the complement system, the imbalance of which is the pathophysiological mechanism of acne.

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