Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 720
Filter
1.
Chinese Medical Journal ; (24): 130-139, 2024.
Article in English | WPRIM | ID: wpr-1007670

ABSTRACT

Small cell lung cancer (SCLC) is a highly malignant tumor with a very poor prognosis; therefore, more effective treatments are urgently needed for patients afflicted with the disease. In recent years, emerging molecular classifications based on key transcription factors of SCLC have provided more information on the tumor pathophysiology, metastasis, immune microenvironment, and acquired therapeutic resistance and reflected the intertumoral heterogeneity of the various SCLC phenotypes. Additionally, advances in genomics and single-cell sequencing analysis have further revealed the high intratumoral heterogeneity and plasticity of the disease. Herein, we review and summarize these recent lines of evidence and discuss the possible pathogenesis of SCLC.


Subject(s)
Humans , Small Cell Lung Carcinoma/genetics , Lung Neoplasms/genetics , Prognosis , Genomics , Phenotype , Tumor Microenvironment
2.
Article in Chinese | WPRIM | ID: wpr-1009359

ABSTRACT

OBJECTIVE@#To explore the genetic basis for a fetus with Cardiac valvular dysplasia type 1 (CVDP1).@*METHODS@#A CVDP1 fetus identified at the Ningbo Women and Children's Hospital on July 7, 2022 was selected as the study subject. Clinical data of the fetus was collected. The fetus and its parents were subjected to trio-whole exome sequencing (trio-WES), and candidate variants were verified by Sanger sequencing.@*RESULTS@#The fetus had exhibited generalized edema, complex cardiac malformation, abdominal effusion, and enhanced intestinal and renal parenchymal echoes. Trio-WES revealed that it has harbored compound heterozygous variants of the PLD1 gene, namely c.2977C>T (p.R993*) and c.1460G>A (p.W487*), which were respectively inherited from its father and mother. Neither variant was reported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.2977C>T (p.R993*) variant was evaluated to be likely pathogenic (PVS1_Moderate+PM2_Supporting+PM3+PP4), whilst the c.1460G>A (p.W487*) variant was evaluated to be pathogenic (PVS1+PM2_Supporting+PP4).@*CONCLUSION@#The c.2977C>T (p.R993*) and c.1460G>A (p.W487*) compound heterozygous variants of the PLD1 gene probably underlay the CVDP1 in the fetus. Above discovery has enriched the mutational spectrum of the PLD1 gene and provided a guidance for genetic counseling and prenatal diagnosis in this family.


Subject(s)
Child , Pregnancy , Humans , Female , Fetus , Genetic Counseling , Genomics , Kidney , Mutation , Phenotype
3.
Med. infant ; 30(2): 204-213, Junio 2023. ilus, tab
Article in Spanish | LILACS, UNISALUD, BINACIS | ID: biblio-1443868

ABSTRACT

El Hospital Garrahan ha sido pionero en el diagnóstico molecular de patologías pediátricas en Argentina. Los avances tecnológicos de las últimas décadas en el área de la biología molecular, sentaron las bases para la optimización y ampliación del diagnóstico molecular a partir de la secuenciación masiva en paralelo de múltiples genes. El presente trabajo describe el proceso de implementación de los estudios de secuenciación de nueva generación y el desarrollo de la Unidad de Genómica en un hospital público pediátrico de alta complejidad, así como su impacto en las capacidades diagnósticas de enfermedades poco frecuentes de origen genético. La creación del Grupo Interdisciplinario de Estudios Genómicos constituyó la vía institucional para la toma de decisiones que implican la implementación de nuevos estudios genómicos y el establecimiento de prioridades diagnósticas, extendiendo la disponibilidad del diagnóstico molecular a más disciplinas. La Unidad de Genómica trabaja en diseñar las estrategias que permitan la mayor optimización de los recursos con los que cuenta el hospital, teniendo en cuenta el equipamiento disponible, las prioridades establecidas y la frecuencia de las distintas patologías. Se demuestra el salto significativo operado en nuestras capacidades diagnósticas, tanto en la variedad de enfermedades como en el número de genes analizados, habiendo estudiado a la fecha alrededor de 2.000 pacientes, muchos de los cuales ven de este modo finalizada su odisea diagnóstica. Los estudios de NGS se han convertido en una herramienta de la práctica diaria para la atención de un número importante de pacientes de nuestro hospital. Continuaremos trabajando para ampliar su aplicación a la mayor cantidad de patologías, a través de los mecanismos institucionales ya existentes (AU)


The Garrahan Hospital has been a pioneer in the molecular diagnosis of pediatric diseases in Argentina. The technological advances of the last decades in the area of molecular biology have laid the foundations for the optimization and expansion of molecular diagnostics through massive parallel sequencing of multiple genes. This study describes the process of implementation of next-generation sequencing studies and the development of the Genomics Unit in a public pediatric tertiary hospital, and its impact on the capacity to diagnose rare diseases of genetic origin. The creation of the Interdisciplinary Group of Genomic Studies constituted the institutional pathway for decision-making involving the implementation of new genomic studies and the establishment of diagnostic priorities, extending the availability of molecular diagnostics to additional disciplines. The Genomics Unit is working to design strategies that allow for optimization of the resources available to the hospital, taking into account the equipment available, the priorities established, and the frequency of the different diseases. It demonstrates the significant leap in our diagnostic capabilities, both in the variety of diseases and in the number of genes analyzed. To date, around 2,000 patients have been studies, many of whom have thus completed their diagnostic odyssey. NGS studies have become a tool in daily practice for the care of a significant number of patients in our hospital. We will continue working to expand its application to as many diseases as possible, through the existing institutional mechanisms (AU)


Subject(s)
Humans , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Genomics/instrumentation , Molecular Diagnostic Techniques/methods , High-Throughput Nucleotide Sequencing , Genomic Medicine/trends , Genetic Diseases, Inborn/diagnosis , Laboratories, Hospital , Hospitals, Pediatric
5.
Frontiers of Medicine ; (4): 1135-1169, 2023.
Article in English | WPRIM | ID: wpr-1010825

ABSTRACT

Pancreatic cancer, notorious for its late diagnosis and aggressive progression, poses a substantial challenge owing to scarce treatment alternatives. This review endeavors to furnish a holistic insight into pancreatic cancer, encompassing its epidemiology, genomic characterization, risk factors, diagnosis, therapeutic strategies, and treatment resistance mechanisms. We delve into identifying risk factors, including genetic predisposition and environmental exposures, and explore recent research advancements in precursor lesions and molecular subtypes of pancreatic cancer. Additionally, we highlight the development and application of multi-omics approaches in pancreatic cancer research and discuss the latest combinations of pancreatic cancer biomarkers and their efficacy. We also dissect the primary mechanisms underlying treatment resistance in this malignancy, illustrating the latest therapeutic options and advancements in the field. Conclusively, we accentuate the urgent demand for more extensive research to enhance the prognosis for pancreatic cancer patients.


Subject(s)
Humans , Pancreatic Neoplasms/therapy , Prognosis , Pancreas/pathology , Genetic Predisposition to Disease , Genomics
6.
Frontiers of Medicine ; (4): 889-906, 2023.
Article in English | WPRIM | ID: wpr-1010805

ABSTRACT

Primary central nervous system lymphoma (PCNSL) is an uncommon non-Hodgkin's lymphoma with poor prognosis. This study aimed to depict the genetic landscape of Chinese PCNSLs. Whole-genome sequencing was performed on 68 newly diagnosed Chinese PCNSL samples, whose genomic characteristics and clinicopathologic features were also analyzed. Structural variations were identified in all patients with a mean of 349, which did not significantly influence prognosis. Copy loss occurred in all samples, while gains were detected in 77.9% of the samples. The high level of copy number variations was significantly associated with poor progression-free survival (PFS) and overall survival (OS). A total of 263 genes mutated in coding regions were identified, including 6 newly discovered genes (ROBO2, KMT2C, CXCR4, MYOM2, BCLAF1, and NRXN3) detected in ⩾ 10% of the cases. CD79B mutation was significantly associated with lower PFS, TMSB4X mutation and high expression of TMSB4X protein was associated with lower OS. A prognostic risk scoring system was also established for PCNSL, which included Karnofsky performance status and six mutated genes (BRD4, EBF1, BTG1, CCND3, STAG2, and TMSB4X). Collectively, this study comprehensively reveals the genomic landscape of newly diagnosed Chinese PCNSLs, thereby enriching the present understanding of the genetic mechanisms of PCNSL.


Subject(s)
Humans , DNA Copy Number Variations , Nuclear Proteins/genetics , Central Nervous System Neoplasms/pathology , Transcription Factors/genetics , Prognosis , Lymphoma/genetics , Genomics , China , Central Nervous System/pathology , Bromodomain Containing Proteins , Cell Cycle Proteins/genetics
7.
Chinese Journal of Biotechnology ; (12): 1314-1331, 2023.
Article in Chinese | WPRIM | ID: wpr-981140

ABSTRACT

Stenotrophomonas species are non-fermentative Gram-negative bacteria that are widely distributed in environment and are highly resistant to numerous antibiotics. Thus, Stenotrophomonas serves as a reservoir of genes encoding antimicrobial resistance (AMR). The detection rate of Stenotrophomonas is rapidly increasing alongside their strengthening intrinsic ability to tolerate a variety of clinical antibiotics. This review illustrated the current genomics advances of antibiotic resistant Stenotrophomonas, highlighting the importance of precise identification and sequence editing. In addition, AMR diversity and transferability have been assessed by the developed bioinformatics tools. However, the working models of AMR in Stenotrophomonas are cryptic and urgently required to be determined. Comparative genomics is envisioned to facilitate the prevention and control of AMR, as well as to gain insights into bacterial adaptability and drug development.


Subject(s)
Stenotrophomonas/genetics , Drug Resistance, Bacterial/genetics , Anti-Bacterial Agents/pharmacology , Gram-Negative Bacteria , Genomics , Microbial Sensitivity Tests
8.
Article in Chinese | WPRIM | ID: wpr-969900

ABSTRACT

Objective: To characterize the prevalence and genomic epidemiology of Vibrio parahaemolyticus from acute diarrheal patients in Shenzhen City from 2013 to 2021. Methods: Based on the Shenzhen Infectious Diarrhea Surveillance System, acute diarrheal patients were actively monitored in sentinel hospitals from 2013 to 2021. Whole-genome sequencing (WGS) of Vibrio parahaemolyticus isolates was performed, and the genomic population structure, serotypes, virulence genes and multilocus sequence typing were analyzed. Outbreak clusters from 2019 to 2021 were explored based on single-nucleotide polymorphism analysis. Results: A total of 48 623 acute diarrhea cases were monitored in 15 sentinel hospitals from 2013 to 2021, and 1 135 Vibrio parahaemolyticus strains were isolated, with a positive isolation rate of 2.3%. Qualified whole-genome sequencing data of 852 isolates were obtained. Eighty-nine serotypes, 21 known ST types and 5 new ST types were identified by sequence analysis, and 93.2% of strains were detected with toxin profile of tdh+trh-. 8 clonal groups (CGs) were captured, with CG3 as the absolute predominance, followed by CG189. The CG3 group was dominated by O3:K6 serotype and ST3 sequence type, while CG189 group was mainly O4:KUT, O4:K8 serotypes and ST189a and ST189 type. A total of 13 clusters were identified, containing 154 cases. About 30 outbreak clusters with 29 outbreak clusters caused by CG3 strains from 2019 to 2021. Conclusion: Vibrio parahaemolyticus is a major pathogen of acute infectious diarrhea in Shenzhen City, with diverse population structures. CG3 and CG189 have been prevalent and predominant in Shenzhen City for a long time. Scattered outbreaks and persistent sources of contamination ignored by traditional methods could be captured by WGS analysis. Tracing the source of epidemic clone groups and taking precise prevention and control measures are expected to significantly reduce the burden of diarrhea diseases caused by Vibrio parahaemolyticus infection in Shenzhen City.


Subject(s)
Humans , Vibrio parahaemolyticus/genetics , Diarrhea/epidemiology , Foodborne Diseases/epidemiology , Serogroup , Genomics , Dysentery , Vibrio Infections/epidemiology , Serotyping
9.
Article in Chinese | WPRIM | ID: wpr-969880

ABSTRACT

With the determination of the whole genome sequence of varicella-zoster virus (VZV) virus, the successful breakthrough of infectious cloning technology of VZV, and the emergence of effective preventive vaccines, which have been proven to be effective and safe, varicella has become a disease preventable by specific immunity. This article will review the genomic structure, epidemiological characteristics, and research application progress of varicella vaccine and herpes zoster vaccine of varicella zoster virus to provide reference for primary prevention of the disease.


Subject(s)
Humans , Herpesvirus 3, Human/genetics , Herpes Zoster/prevention & control , Herpes Zoster Vaccine , Chickenpox Vaccine , Genomics
10.
Article in English | WPRIM | ID: wpr-969666

ABSTRACT

Advancements in high-throughput sequencing have yielded vast amounts of genomic data, which are studied using genome-wide association study (GWAS)/phenome-wide association study (PheWAS) methods to identify associations between the genotype and phenotype. The associated findings have contributed to pharmacogenomics and improved clinical decision support at the point of care in many healthcare systems. However, the accumulation of genomic data from sequencing and clinical data from electronic health records (EHRs) poses significant challenges for data scientists. Following the rise of artificial intelligence (AI) technology such as machine learning and deep learning, an increasing number of GWAS/PheWAS studies have successfully leveraged this technology to overcome the aforementioned challenges. In this review, we focus on the application of data science and AI technology in three areas, including risk prediction and identification of causal single-nucleotide polymorphisms, EHR-based phenotyping and CRISPR guide RNA design. Additionally, we highlight a few emerging AI technologies, such as transfer learning and multi-view learning, which will or have started to benefit genomic studies.


Subject(s)
Artificial Intelligence , Data Science , Genome-Wide Association Study , Genomics , Technology
11.
Chinese Medical Journal ; (24): 910-921, 2023.
Article in English | WPRIM | ID: wpr-980842

ABSTRACT

The prevalence of obesity has increased worldwide in recent decades. Genetic factors are now known to play a substantial role in the predisposition to obesity and may contribute up to 70% of the risk for obesity. Technological advancements during the last decades have allowed the identification of many hundreds of genetic markers associated with obesity. However, the transformation of current genetic variant-obesity associations into biological knowledge has been proven challenging. Genomics and proteomics are complementary fields, as proteomics extends functional analyses. Integrating genomic and proteomic data can help to bridge a gap in knowledge regarding genetic variant-obesity associations and to identify new drug targets for the treatment of obesity. We provide an overview of the published papers on the integrated analysis of proteomic and genomic data in obesity and summarize four mainstream strategies: overlap, colocalization, Mendelian randomization, and proteome-wide association studies. The integrated analyses identified many obesity-associated proteins, such as leptin, follistatin, and adenylate cyclase 3. Despite great progress, integrative studies focusing on obesity are still limited. There is an increased demand for large prospective cohort studies to identify and validate findings, and further apply these findings to the prevention, intervention, and treatment of obesity. In addition, we also discuss several other potential integration methods.


Subject(s)
Humans , Proteome/metabolism , Proteomics , Prospective Studies , Obesity/genetics , Genomics , Genome-Wide Association Study
12.
Chinese Medical Journal ; (24): 2621-2631, 2023.
Article in English | WPRIM | ID: wpr-1007549

ABSTRACT

BACKGROUND@#The molecular mechanisms driving tumorigenesis have continually been the focus of researchers. Cuproplasia is defined as copper-dependent cell growth and proliferation, including its primary and secondary roles in tumor formation and proliferation through signaling pathways. In this study, we analyzed the differences in the expression of cuproplasia-associated genes (CAGs) in pan-cancerous tissues and investigated their role in immune-regulation and tumor prognostication.@*METHODS@#Raw data from 11,057 cancer samples were acquired from multiple databases. Pan-cancer analysis was conducted to analyze the CAG expression, single-nucleotide variants, copy number variants, methylation signatures, and genomic signatures of micro RNA (miRNA)-messenger RNA (mRNA) interactions. The Genomics of Drug Sensitivity in Cancer and the Cancer Therapeutics Response Portal databases were used to evaluate drug sensitivity and resistance against CAGs. Using single-sample Gene Set Enrichment Analysis (ssGSEA) and Immune Cell Abundance Identifier database, immune cell infiltration was analyzed with the ssGSEA score as the standard.@*RESULTS@#Aberrantly expressed CAGs were found in multiple cancers. The frequency of single-nucleotide variations in CAGs ranged from 1% to 54% among different cancers. Furthermore, the correlation between CAG expression in the tumor microenvironment and immune cell infiltration varied among different cancers. ATP7A and ATP7B were negatively correlated with macrophages in 16 tumors including breast invasive carcinoma and esophageal carcinoma, while the converse was true for MT1A and MT2A . In addition, we established cuproplasia scores and demonstrated their strong correlation with patient prognosis, immunotherapy responsiveness, and disease progression ( P  <0.05). Finally, we identified potential candidate drugs by matching gene targets with existing drugs.@*CONCLUSIONS@#This study reports the genomic characterization and clinical features of CAGs in pan-cancers. It helps clarify the relationship between CAGs and tumorigenesis, and may be helpful in the development of biomarkers and new therapeutic agents.


Subject(s)
Humans , Female , Genomics , Carcinogenesis , Carcinoma , Breast Neoplasms , Cell Transformation, Neoplastic , Nucleotides , Tumor Microenvironment
13.
Article in Chinese | WPRIM | ID: wpr-1009340

ABSTRACT

OBJECTIVE@#To explore the genetic basis for a child featuring facial dysmorphism, single palmar crease, motor and language delay, and hypoplasia of corpus callosum.@*METHODS@#A child who had visited the Affiliated Hospital of Binzhou Medical College on March 16, 2021 was selected as the study subject. Peripheral blood samples of the child and his parents were collected, and the genomic DNA was extracted for whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#WES revealed that the child has harbored a heterozygous c.607delT (p.S203Pfs*31) variant in exon 9 of the TCF4 gene, for which both of his parents were of the wild-type. Based on guidelines from the American College of Medical Genetics and Genomics, the variant was classified as pathogenic (PVS1+PM2_Supporting+PM6).@*CONCLUSION@#The heterozygous c.607delT (p.S203Pfs*31) variant of the TCF4 gene probably underlay the Pitt-Hopkins syndrome in this child. Genetic testing has enabled the definite diagnosis.


Subject(s)
Humans , Child , Exons , Computational Biology , Genetic Testing , Genomics , Mutation
14.
Article in Chinese | WPRIM | ID: wpr-1009336

ABSTRACT

OBJECTIVE@#To explore the clinical phenotype and genetic variant in a child with Verheij syndrome (VRJS).@*METHODS@#A child who had presented at the Soochow University Affiliated Children's Hospital and Wujiang District Children's Hospital in July 2022 for "elevated scapula since early childhood" was selected as the study subject. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The child had manifested elevated scapulae, torticollis, neck asymmetry, facial dysmorphism, dispersed café-au-lait spots, limited mobility of upper limbs and shoulder joints, and intellectual disability. Sequencing revealed that he has harbored a de novo heterozygous c.405dupT (p.Ile136Tyrfs*4) variant of the PUF60 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), this variant was classified as pathogenic (PVS1+PS2_moderate+PM2_supporting). Combined his clinical features and result of genetic testing, the child was diagnosed with VRJS due to variant of the PUF60 gene.@*CONCLUSION@#The clinical manifestations of VRJS include facial dysmorphism, intellectual disability, elevated scapulae, vertebral fusion, other skeletal malformations, without significant abnormalities of the heart, kidney, and eyes, which need to be distinguished from Klippel-Feil syndrome. Above finding has expended the mutation spectrum of the PUF60 gene and provided a reference for delineation of the genotype-phenotype correlation of the VRJS.


Subject(s)
Child , Child, Preschool , Humans , Male , Cafe-au-Lait Spots , Computational Biology , Genetic Testing , Genomics , Intellectual Disability/genetics , Mutation
15.
Article in Chinese | WPRIM | ID: wpr-1009333

ABSTRACT

OBJECTIVE@#To explore the clinical characteristics and genetic variants in two children with Tuberous sclerosis complex (TSC).@*METHODS@#Two children who had presented at the Children's Hospital Affiliated to Zhengzhou University respectively in June 2020 and July 2021 were selected as the study subjects. Clinical data of the children were collected, and potential pathogenic variants were screened by whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing of their family members.@*RESULTS@#Child 1 was a 7-month-and-29-day-old male, and child 2 was a 2-year-and-6-month-old male. Both children had shown symptoms of epileptic seizures and multiple hypomelanotic macules. Genetic testing revealed that both children had harbored de novo variants of the TSC2 gene, namely c.3239_3240insA and c.3330delC, which were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as pathogenic (PVS1+PS2+PM2_Supporting).@*CONCLUSION@#This study has uncovered the genetic etiology for two children with TSC. Above findings have also enriched the phenotypic and mutational spectrum of TSC in the Chinese population.


Subject(s)
Humans , Infant , Male , Child, Preschool , Family , Genetic Testing , Genomics , Mutation , Tuberous Sclerosis/genetics , East Asian People
16.
Article in Chinese | WPRIM | ID: wpr-1009298

ABSTRACT

OBJECTIVE@#To explore the genetic etiology for a fetus with hydrocephalus and intraventricular hemorrhage.@*METHODS@#Trio whole exome sequencing was carried out. Candidate variants were verified by Sanger sequencing of the fetus and its parents.@*RESULTS@#The fetus was found to harbor c.818G>A (p.W273X) and c.833T>C (p.L278P) compound heterozygous variants of the PROC gene, which were respectively inherited from its mother and father. Based on the guidelines of the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be likely pathogenic (PVS1_Strong+PM2_Supporting+PP4; PM2_Supporting+PM3+PP1+PP3+PP4).@*CONCLUSION@#The fetus was diagnosed with Protein C deficiency due to the c.818G>A (p.W273X) and c.833T>C (p.L278P) compound heterozygous variants of the PROC gene. Above finding has enriched the spectrum of PROC gene variants and enabled genetic counseling and prenatal diagnosis for the family.


Subject(s)
Female , Pregnancy , Humans , Protein C Deficiency , Fetus , Genetic Counseling , Genomics , Hydrocephalus/genetics , Mutation
17.
Article in Chinese | WPRIM | ID: wpr-1009294

ABSTRACT

OBJECTIVE@#To explore the genetic basis for a child with optic atrophy and global developmental delay.@*METHODS@#A child who had presented at the Guangzhou Women and Children's Medical Center in January 2022 was selected as the study subject. Clinical data were collected. Whole exome sequencing (WES) was carried out for the child. Candidate variant was validated by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The child, a nine-month-old female, had manifested dysopia and global developmental delay. Genetic testing revealed that she has harbored a de novo c.425G>C (p.Arg142Pro) variant of the NR2F1 gene, which has been associated with Bosch-Boonstra-Schaaf syndrome. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PS2+PM1+PM2_Supporting+PM5+PP3+PP4).@*CONCLUSION@#The c.425G>C (p.Arg142Pro) variant of the NR2F1 gene probably underlay the pathogenesis in this child. Above finding has enriched the genotypic and phenotypic spectrum of the NR2F1 gene.


Subject(s)
Female , Humans , Infant , Computational Biology , COUP Transcription Factor I/genetics , Genetic Testing , Genomics , Genotype , Optic Atrophy/genetics
18.
Article in Chinese | WPRIM | ID: wpr-1009289

ABSTRACT

OBJECTIVE@#To analyze the clinical phenotype and genetic variant in a child with Raynaud-Claes syndrome (RCS).@*METHODS@#A child who was diagnosed with RCS at the Children's Hospital Affiliated to Zhengzhou University for delayed language and motor development in August 2022 was selected as the study subject. Clinical data of the child were collected, and potential genetic variant was detected by next-generation sequencing and Sanger sequencing. The pathogenicity of the candidate variant was analyzed.@*RESULTS@#The child, a 4-year-and-4-month-old male, has manifested global developmental delay, speech disorders, special facial features and behavioral abnormalities. Genetic testing revealed that he has harbored a hemizygous c.1174C>T (p.Gln392Ter) variant of the CLCN4 gene, which was not detected in either of his parents. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic (PVS1+PS2+PM2_Supporting).@*CONCLUSION@#The c.1174C>T (p.Gln392Ter) variant of the CLCN4 gene probably underlay the PCS in this child. Above finding has expanded the mutational spectrum of the CLCN4 gene and enabled genetic counseling and prenatal diagnosis for his family.


Subject(s)
Female , Humans , Male , Pregnancy , Child, Preschool , Chloride Channels/genetics , Genetic Counseling , Genetic Testing , Genomics , High-Throughput Nucleotide Sequencing , Mutation
19.
Article in Chinese | WPRIM | ID: wpr-1009288

ABSTRACT

OBJECTIVE@#To explore the clinical features and genetic etiology of a patient with primary distal renal tubular acidosis (dRTA).@*METHODS@#A child who was diagnosed with primary dRTA at the Xi'an Children's Hospital in April 2021 due to poor appetite and persistent crying was selected as the study subject. Clinical data of the patient was collected. Whole exome sequencing (WES) was carried out for the child. Candidate variants were validated by Sanger sequencing of his family members.@*RESULTS@#The child, a 1-month-and-18-day male, had featured poor appetite, persistent crying, poor weight gain and dehydration. Laboratory examination has suggested metabolic acidosis, hyperchloremia, hypokalemia, abnormal alkaline urine and anemia. Ultrasonographic examination of the urinary system revealed calcium deposition in renal medulla. DNA sequencing revealed that he has harbored compound heterozygous variants of the ATP6V0A4 gene, namely c.1363dupA (p.M455NfsX14) and c.2257C>T (p.Q753X), which were respectively inherited from his father and mother. Based on the guidelines from the American College of Medical Genetics and Genomics, both variants were classified as pathogenic (PVS1+PM3+PM2_Supporting).@*CONCLUSION@#The compound heterozygous variants of c.1363dupA (p.M455NfsX14) and c.2257C>T (p.Q753X) of the ATP6V0A4 gene probably underlay the pathogenesis of primary dRTA in this patient. Discovery of the c.2257C>T (p.Q753X) variant has also expanded the mutational spectrum of the ATP6V0A4 gene.


Subject(s)
Humans , Male , Infant , Acidosis, Renal Tubular/genetics , Family , Genomics , Hypokalemia
20.
Article in Chinese | WPRIM | ID: wpr-1009287

ABSTRACT

OBJECTIVE@#To investigate the clinical features and genetic variant of a child with X-linked dominant Alport syndrome (XLAS).@*METHODS@#A child who had presented at the First Affiliated Hospital of Zhengzhou University in May 2019 was selected as the study subject. Clinical data of the child was collected. Next generation sequencing (NGS) was carried out for the child. Candidate variants were validated by Sanger sequencing of his family members.@*RESULTS@#The child, a 12-year-old boy, had mainly manifested gross hematuria, proteinuria, nephrotic syndrome, and progressive renal impairment in conjunct with hearing loss. Kidney biopsy has revealed uneven glomerular basement membrane thickness. DNA sequencing revealed that the child and his mother have both carried a heterozygous c.2632G>A (p.G878R) variant of the COL4A5 gene, for which his father and brother were of the wild type. This variant was unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was classified as pathogenic (PS1+PM1+PM2_Supporting+PP3).@*CONCLUSION@#The maternally derived hemizygous c.2632G>A (p.G878R) variant of the COL4A5 gene probably underlay the XLAS in this child. Above finding has enriched the mutational spectrum of the COL4A5 gene.


Subject(s)
Male , Female , Humans , Child , Nephritis, Hereditary/genetics , Deafness , Kidney Glomerulus , Genomics , Mothers
SELECTION OF CITATIONS
SEARCH DETAIL