1.Application of live biotherapeutic products and perspective in the treatment of inherited metabolic disease.
Zhaowei CHEN ; Min GUO ; Huajun ZHENG
Chinese Journal of Biotechnology 2023;39(4):1290-1303
Live biotherapeutic products (LBPs) refer to the living bacteria derived from human body intestinal gut or in nature that can be used to treat the human disease. However, the naturally screened living bacteria have some disadvantages, such as deficient therapeutic effect and great divergence, which fall short of the personalized diagnosis and treatment needs. In recent years, with the development of synthetic biology, researchers have designed and constructed several engineered strains that can respond to external complex environmental signals, which speeded up the process of development and application of LBPs. Recombinant LBPs modified by gene editing can have therapeutic effect on specific diseases. Inherited metabolic disease is a type of disease that causes a series of clinical symptoms due to the genetic defect of some enzymes in the body, which may cause abnormal metabolism the corresponding metabolites. Therefore, the use of synthetic biology to design LBPs targeting specific defective enzymes will be promising for the treatment of inherited metabolic defects in the future. This review summarizes the clinic applications of LBPs and its potential for the treatment of inherited metabolic defects.
Humans
;
Bacteria/genetics*
;
Gene Editing
;
Metabolic Diseases/therapy*
2.Research progress on hereditary endocrine and metabolic diseases associated with sensorineural hearing loss.
Fang CHEN ; Qinying ZHANG ; Qiujing ZHANG ; Qiuju WANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2024;38(1):63-69
Hereditary endocrine and metabolic diseases , caused by genetic factors, exhibit complex and diverse symptoms, including the possibility of concurrent sensorineural deafness. Currently, there is a limited clinical understanding of hereditary endocrine and metabolic diseases that manifest with deafness, the pathogenesis remains unclear,and there is a lack of effective diagnostic and treatment methods. This article summarizes the research progress of hereditary endocrine and metabolic diseases complicated with deafness from the pathogenesis, clinical phenotype, diagnosis and treatment. Understanding the current research progress and integrating genetic analysis into clinical practice are crucial for accurate diagnosis and treatment, evaluating clinical efficacy, and providing effective genetic counseling for these diseases.
Humans
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Deafness/genetics*
;
Hearing Loss, Sensorineural/diagnosis*
;
Phenotype
;
Metabolic Diseases/genetics*
;
Genetic Counseling
3.Advances in research on the clinical phenotype and genetic etiology of jaundice associated with Hereditary bilirubin metabolic disorders.
Chinese Journal of Medical Genetics 2023;40(11):1436-1440
Hereditary bilirubin metabolic disorder is an important cause for jaundice. For its diverse types and similar clinical manifestations, it has been difficult to make a clear etiological diagnosis. The application of next generation sequencing in recent years has delineated the more and more genetic etiologies for jaundice. This article has reviewed the clinical manifestations and genetic etiology of bilirubin metabolic disorder jaundice, with an aim to enhance the understanding of such diseases and facilitate their clinical diagnosis and treatment, which will provide a reference for genetic counseling and/or prenatal diagnosis for the affected individuals and families.
Female
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Pregnancy
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Humans
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Metabolic Diseases/genetics*
;
Jaundice/genetics*
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Bilirubin
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Genetic Counseling
;
Phenotype
4.Analysis of CGDH gene variants and clinical features in three patients with glutaric aciduria type Ⅰ.
Jianqiang TAN ; Dayu CHEN ; Tizhen YAN ; Jun HUANG ; Ren CAI
Chinese Journal of Medical Genetics 2019;36(9):882-885
OBJECTIVE:
To screen for potential variants of GCDH gene in 3 patients clinically diagnosed as glutaric aciduria type Ⅰ.
METHODS:
GCDH gene variants was detected by Sanger sequencing among the three children and their family members.
RESULTS:
Sanger sequencing showed that patient 1 carried compound heterozygosity variants of c.532G>A (p.Gly178Arg) and c.655G>A (p.Ala219Thr) of the GCDH gene, while his father and mother respectively carried heterozygous c.532G>A(p.Gly178Arg) and c.655G>A (p.Ala219Thr) variants. Patient 2 carried c.532G>A (p.Gly178Arg) and a novel c.1060G>T (p.Gly354Cys) compound heterozygous variant, while his father and mother respectively carried heterozygous c.532G>A (p.Gly178Arg) and c.1060G>T (p.Gly354Cys) variant. Patient 3 carried homozygous c.532G>A (p.Gly178Arg) variant of the GCDH gene, for which both of his parents were heterozygous carriers.
CONCLUSION
The GCDH gene variant probably underlie the glutaric aciduria type Ⅰ among the 3 patients. Identifcation of the novel variant has enriched the spectrum of GCDH gene variants.
Amino Acid Metabolism, Inborn Errors
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genetics
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Brain Diseases, Metabolic
;
genetics
;
Female
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Glutaryl-CoA Dehydrogenase
;
deficiency
;
genetics
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Heterozygote
;
Humans
;
Male
5.Clinical phenotype and novel mutation in one of twins with glutaric acidemia type I.
Ying WANG ; Shujun FU ; Yuqi YANG ; Huaiyan WANG ; Yuping ZHANG ; Hong ZHOU ; Bin YU
Chinese Journal of Medical Genetics 2019;36(6):602-605
OBJECTIVE:
To review the clinical features of a male twin affected with glutaric academia type I (GA-I) and analyze the variations of glutaryl-CoA dehydrogenase (GCDH) gene.
METHODS:
Clinical data of the pair of twins and their parents were collected. Genomic DNA was extracted from peripheral blood samples, and variants of GCDH genes were detected by capture sequencing using a customized panel. Variants of the twins and their parents were verified by Sanger sequencing.
RESULTS:
The level of glutaric acyl carnitine (C5DC + C6OH) was 3.26 μmol/L in the male twin. The relative level of glutaric acid in urine was 547.51 by gas chromatography mass spectrometry analysis. Cerebral ultrasonography showed that the patient had subependymal hemorrhage, but no serious clinical manifestation was noted. After treating with special formula milk powder and L-carnitine, the boy showed good growth and development. Two heterozygous variants of the GCDH gene were detected in the patient, among which c.416C>G was suspected to be pathogenic, while c.109_110delCA was unreported. The variants were respectively inherited from his parents. The twin girl only carried the c.416C>G variant.
CONCLUSION
GA-I can be diagnosed by mass spectrometry, urine gas chromatographic mass spectrometry, imaging as well as genetic diagnosis. Early diagnosis and intervention is important.
Amino Acid Metabolism, Inborn Errors
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genetics
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Brain Diseases, Metabolic
;
genetics
;
Female
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Glutaryl-CoA Dehydrogenase
;
deficiency
;
genetics
;
Humans
;
Male
;
Mutation
;
Phenotype
7.Clinical characterization and genetic testing for a patient with creatine deficiency syndrome 1.
Shu XYU ; Chen XU ; Yuan LYU ; Chuang LI ; Caixia LIU
Chinese Journal of Medical Genetics 2022;39(2):213-215
OBJECTIVE:
To explore the genetic basis for a child affected with cerebral creatine deficiency syndrome 1 (CCDS1).
METHODS:
High-throughput sequencing was carried out to screen pathogenic variant associated with the clinical phenotype of the proband. The candidate variant was verified by Sanger sequencing.
RESULTS:
High-throughput sequencing revealed that the proband has carried heterozygous c.327delG variant of the SLC6A8 gene, which was verified by Sanger sequencing.Neither parent was found to carry the same variant.
CONCLUSION
The de novo heterozygous c.327delG variant of the SLC6A8 gene probably underlay the CCDS1 in this child.
Brain Diseases, Metabolic, Inborn/genetics*
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Creatine
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Genetic Testing
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Heterozygote
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Humans
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Mental Retardation, X-Linked
;
Mutation
8.Expert consensus on the follow-up of newborn screening for neonatal genetic and metabolic diseases.
COMMITTEE FOR PROFICIENCY TESTING NEONATAL GENETIC METABOLIC DISEASE SCREENING CENTER NATIONAL HEALTH COMMISSION OF CHINA ; Mingcai OU ; Jianhui JIANG ; Zhiguo WANG
Chinese Journal of Medical Genetics 2020;37(4):367-372
Follow-up is a crucial step for the screening of neonatal genetic and metabolic diseases, which can directly influence the detection, diagnosis, efficacy of treatment, as well as the quality of neonatal screening. In view of the lack of follow-up, full understanding, and inconsistent requirement between various agencies and personnel in China, there is an urgent need for standardization. The Committee for Proficiency Testing of the Neonatal Genetic Metabolic Disease Screening Center of the National Health Committee of China has organized the writing of expert consensus for follow-up of neonatal genetic and metabolic disease screening after thorough discussion, so as to guide the follow-up work and improve its quality.
China
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Consensus
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Follow-Up Studies
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Genetic Diseases, Inborn
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diagnosis
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Humans
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Infant, Newborn
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Metabolic Diseases
;
diagnosis
;
genetics
;
Neonatal Screening
9.A descriptive analysis of hyperlipidemia in adult twins in China.
Ke MIAO ; Wei Hua CAO ; Jun LYU ; Can Qing YU ; Sheng Feng WANG ; Tao HUANG ; Dian Jian Yi SUN ; Chun Xiao LIAO ; Yuan Jie PANG ; Zeng Chang PANG ; Min YU ; Hua WANG ; Xian Ping WU ; Zhong DONG ; Fan WU ; Guo Hong JIANG ; Xiao Jie WANG ; Yu LIU ; Jian DENG ; Lin LU ; Wen Jing GAO ; Li Ming LI
Chinese Journal of Epidemiology 2023;44(4):544-551
Objective: To describe the distribution characteristics of hyperlipidemia in adult twins in the Chinese National Twin Registry (CNTR) and explore the effect of genetic and environmental factors on hyperlipidemia. Methods: Twins recruited from the CNTR in 11 project areas across China were included in the study. A total of 69 130 (34 565 pairs) of adult twins with complete information on hyperlipidemia were selected for analysis. The random effect model was used to characterize the population and regional distribution of hyperlipidemia among twins. The concordance rates of hyperlipidemia were calculated in monozygotic twins (MZ) and dizygotic twins (DZ), respectively, to estimate the heritability. Results: The age of all participants was (34.2±12.4) years. This study's prevalence of hyperlipidemia was 1.3% (895/69 130). Twin pairs who were men, older, living in urban areas, married,had junior college degree or above, overweight, obese, insufficient physical activity, current smokers, ex-smokers, current drinkers, and ex-drinkers had a higher prevalence of hyperlipidemia (P<0.05). In within-pair analysis, the concordance rate of hyperlipidemia was 29.1% (118/405) in MZ and 18.1% (57/315) in DZ, and the difference was statistically significant (P<0.05). Stratified by gender, age, and region, the concordance rate of hyperlipidemia in MZ was still higher than that in DZ. Further, in within-same-sex twin pair analyses, the heritability of hyperlipidemia was 13.04% (95%CI: 2.61%-23.47%) in the northern group and 18.59% (95%CI: 4.43%-32.74%) in the female group, respectively. Conclusions: Adult twins were included in this study and were found to have a lower prevalence of hyperlipidemia than in the general population study, with population and regional differences. Genetic factors influence hyperlipidemia, but the genetic effect may vary with gender and area.
Adult
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Female
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Humans
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Male
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Middle Aged
;
Young Adult
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China/epidemiology*
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Diseases in Twins/genetics*
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Hyperlipidemias/genetics*
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Metabolic Diseases
;
Twins, Dizygotic
;
Twins, Monozygotic/genetics*
10.Epigenetic effects of human breastfeeding.
Chinese Journal of Contemporary Pediatrics 2016;18(10):926-930
Breastfeeding is well-known for its benefits of preventing communicable and non-communicable diseases. Human breastmilk consists not only of nutrients, but also of bioactive substances. What's more, the epigenetic effects of human breast milk may also play an important role. Alterations in the epigenetic regulation of genes may lead to profound changes in phenotype. Clarifying the role of human breast milk on genetic expression can potentially benefit the infant's health and his later life. This review article makes a brief summary of the epigenetic mechanism of breast milk, and its epigenetic effects on neonatal necrotizing enterocolitis, infectious diseases, metabolism syndrome, cognitive function and anaphylactic diseases.
Breast Feeding
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Cognition
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Communicable Diseases
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etiology
;
genetics
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Enterocolitis, Necrotizing
;
etiology
;
genetics
;
Epigenesis, Genetic
;
Female
;
Humans
;
Hypersensitivity
;
etiology
;
genetics
;
Infant, Newborn
;
Metabolic Syndrome
;
etiology
;
genetics