BACKGROUND Common variable immunodeficiency(CVID)is a primary antibody immunodeficiency disorder characterized by diminished IgG levels.Despite ongoing research,the precise pathogenesis of CVID remains unclear.Genetic...BACKGROUND Common variable immunodeficiency(CVID)is a primary antibody immunodeficiency disorder characterized by diminished IgG levels.Despite ongoing research,the precise pathogenesis of CVID remains unclear.Genetic factors account for only 10%-20%of cases,with an estimated incidence of 1 in 10000 to 1 in 100000,affecting individuals across all age groups.CASE SUMMARY We report the case of a 32-year-old man with CVID who presented with a chief complaint of“recurrent diarrhea and significant weight loss over the past 2 years”.Laboratory tests on admission showed fat droplets in stool,while other parameters were within normal ranges.Gastroscopy revealed a smooth gastric mucosa without bile retention or signs of Helicobacter pylori infection;however,the mucosa of the descending segment of the duodenum appeared rough.Further evaluation of the small intestine using computed tomography indicated no abnormalities.Finally,the whole-small bowel double-balloon enteroscopy(DBE)was performed,which revealed various phenotypic changes in the small intestinal mucosa.The patient was diagnosed with CVID,which improved after immunoglobulin therapy,with favorable follow-up outcomes.CONCLUSION Non-infectious enteropathy in CVID is rare.Therefore,DBE is essential for diagnosing small intestinal involvement in such cases.展开更多
Diabetes mellitus is a complicated disease characterized by a complex interplay of genetic,epigenetic,and environmental variables.It is one of the world's fastestgrowing diseases,with 783 million adults expected t...Diabetes mellitus is a complicated disease characterized by a complex interplay of genetic,epigenetic,and environmental variables.It is one of the world's fastestgrowing diseases,with 783 million adults expected to be affected by 2045.Devastating macrovascular consequences(cerebrovascular disease,cardiovascular disease,and peripheral vascular disease)and microvascular complications(like retinopathy,nephropathy,and neuropathy)increase mortality,blindness,kidney failure,and overall quality of life in individuals with diabetes.Clinical risk factors and glycemic management alone cannot predict the development of vascular problems;multiple genetic investigations have revealed a clear hereditary component to both diabetes and its related complications.In the twenty-first century,technological advancements(genome-wide association studies,nextgeneration sequencing,and exome-sequencing)have led to the identification of genetic variants associated with diabetes,however,these variants can only explain a small proportion of the total heritability of the condition.In this review,we address some of the likely explanations for this"missing heritability",for diabetes such as the significance of uncommon variants,gene-environment interactions,and epigenetics.Current discoveries clinical value,management of diabetes,and future research directions are also discussed.展开更多
SNCA,GBA,and VPS35 are three common genes associated with Parkinson's disease.Previous studies have shown that these three genes may be associated with Alzheimer's disease(AD).However,it is unclear whether the...SNCA,GBA,and VPS35 are three common genes associated with Parkinson's disease.Previous studies have shown that these three genes may be associated with Alzheimer's disease(AD).However,it is unclear whether these genes increase the risk of AD in Chinese populations.In this study,we used a targeted gene sequencing panel to screen all the exon regions and the nearby sequences of GBA,SNCA,and VPS35 in a cohort including 721 AD patients and 365 healthy controls from China.The results revealed that neither common variants nor rare variants of these three genes were associated with AD in a Chinese population.These findings suggest that the mutations in GBA,SNCA,and VPS35 are not likely to play an important role in the genetic susceptibility to AD in Chinese populations.The study was approved by the Ethics Committee of Xiangya Hospital,Central South University,China on March 9,2016(approval No.201603198).展开更多
Parkinson’s disease(PD)is a complex genetic neurodegenerative disorder.Epidemiology genetic discoveries have increased our understanding of the molecular contributors to Parkinson’s pathophysiology,especially when a...Parkinson’s disease(PD)is a complex genetic neurodegenerative disorder.Epidemiology genetic discoveries have increased our understanding of the molecular contributors to Parkinson’s pathophysiology,especially when associated with the advent of genome-wide association studies(GWAS)technologies in the discovery of the risk linked to common germline genetic variants.The biggest limitation of those studies on genetic susceptibility to PD is the lack of information describing the impact of individuals’ancestry on risk associations,especially in non-European populations.Current genetic data are mainly based on individuals of European origin,particularly those included in the UK biobank project.The effects of these ethical discrepancies can directly impact the discovery of risk variants associated with PD susceptibility and clinical management of PD patients in admixture populations,for example.Thus,we performed a PROSPERO-registered systematic review to elucidate the current state of the art about the role of common genetic variants based on GWAS studies in advancing precision medicine for PD susceptibility and pathobiology in multiethnic and non-European populations.Also,we discuss whether there are similarities or discrepancies of these data in relation to genomic data obtained in studies with PD patients of European origin.展开更多
Congenital heart disease(CHD)is observed in up to 1%of live births and is one of the leading causes of mortality from birth defects.While hundreds of genes have been implicated in the genetic etiology of CHD,their rol...Congenital heart disease(CHD)is observed in up to 1%of live births and is one of the leading causes of mortality from birth defects.While hundreds of genes have been implicated in the genetic etiology of CHD,their role in CHD pathogenesis is still poorly understood.This is largely a reflection of the sporadic nature of CHD,as well as its variable expressivity and incomplete penetrance.We reviewed the monogenic causes and evidence for oligogenic etiology of CHD,as well as the role of de novo mutations,common variants,and genetic modifiers.For further mechanistic insight,we leveraged single-cell data across species to investigate the cellular expression characteristics of genes implicated in CHD in developing human and mouse embryonic hearts.Understanding the genetic etiology of CHD may enable the application of precision medicine and prenatal diagnosis,thereby facilitating early intervention to improve outcomes for patients with CHD.展开更多
Genome-wide association studies（GWASs）have revealed a plethora of putative susceptibility genes for Alzheimer＇s disease（AD）. With the sole exception of the APOE gene, these AD susceptibility genes have not been u...Genome-wide association studies（GWASs）have revealed a plethora of putative susceptibility genes for Alzheimer＇s disease（AD）. With the sole exception of the APOE gene, these AD susceptibility genes have not been unequivocally validated in independent studies. No single novel functional risk genetic variant has been identified. In this review, we evaluate recent GWASs of AD, and discuss their significance, limitations, and challenges in the investigation of the genetic spectrum of AD.展开更多
Glutamate receptors and schizophrenia:Schizophrenia is a chronic mental disorder affecting approximately 1%of the global population,with 70%-80%heritability.It has a multifactorial etiology involving both environmenta...Glutamate receptors and schizophrenia:Schizophrenia is a chronic mental disorder affecting approximately 1%of the global population,with 70%-80%heritability.It has a multifactorial etiology involving both environmental factors and a complex polygenic genetic architecture.Over the last two decades,large-scale genome-wide approaches revealed contributions of common variants with individually small effect sizes and of rare copy number variants with a large effect size.N-methy l-D-a spar tat e receptor(NMDAR)hypofunction has been implicated as a central mechanism in the pathophysiology of schizophrenia(Coyle et al.,2020).展开更多
基金Supported by National Natural Science Foundation of China,No.82360120Ten Thousand Doctor Plan in Yunnan Province,No.YNWRMY-2018-020Yunnan Provincial Key Laboratory of Clinical Virology,No.202205AG070053-07.
文摘BACKGROUND Common variable immunodeficiency(CVID)is a primary antibody immunodeficiency disorder characterized by diminished IgG levels.Despite ongoing research,the precise pathogenesis of CVID remains unclear.Genetic factors account for only 10%-20%of cases,with an estimated incidence of 1 in 10000 to 1 in 100000,affecting individuals across all age groups.CASE SUMMARY We report the case of a 32-year-old man with CVID who presented with a chief complaint of“recurrent diarrhea and significant weight loss over the past 2 years”.Laboratory tests on admission showed fat droplets in stool,while other parameters were within normal ranges.Gastroscopy revealed a smooth gastric mucosa without bile retention or signs of Helicobacter pylori infection;however,the mucosa of the descending segment of the duodenum appeared rough.Further evaluation of the small intestine using computed tomography indicated no abnormalities.Finally,the whole-small bowel double-balloon enteroscopy(DBE)was performed,which revealed various phenotypic changes in the small intestinal mucosa.The patient was diagnosed with CVID,which improved after immunoglobulin therapy,with favorable follow-up outcomes.CONCLUSION Non-infectious enteropathy in CVID is rare.Therefore,DBE is essential for diagnosing small intestinal involvement in such cases.
文摘Diabetes mellitus is a complicated disease characterized by a complex interplay of genetic,epigenetic,and environmental variables.It is one of the world's fastestgrowing diseases,with 783 million adults expected to be affected by 2045.Devastating macrovascular consequences(cerebrovascular disease,cardiovascular disease,and peripheral vascular disease)and microvascular complications(like retinopathy,nephropathy,and neuropathy)increase mortality,blindness,kidney failure,and overall quality of life in individuals with diabetes.Clinical risk factors and glycemic management alone cannot predict the development of vascular problems;multiple genetic investigations have revealed a clear hereditary component to both diabetes and its related complications.In the twenty-first century,technological advancements(genome-wide association studies,nextgeneration sequencing,and exome-sequencing)have led to the identification of genetic variants associated with diabetes,however,these variants can only explain a small proportion of the total heritability of the condition.In this review,we address some of the likely explanations for this"missing heritability",for diabetes such as the significance of uncommon variants,gene-environment interactions,and epigenetics.Current discoveries clinical value,management of diabetes,and future research directions are also discussed.
基金supported by the National Natural Science Foundation of China,Nos.81971029 (to LS) and 82071216 (to BJ)。
文摘SNCA,GBA,and VPS35 are three common genes associated with Parkinson's disease.Previous studies have shown that these three genes may be associated with Alzheimer's disease(AD).However,it is unclear whether these genes increase the risk of AD in Chinese populations.In this study,we used a targeted gene sequencing panel to screen all the exon regions and the nearby sequences of GBA,SNCA,and VPS35 in a cohort including 721 AD patients and 365 healthy controls from China.The results revealed that neither common variants nor rare variants of these three genes were associated with AD in a Chinese population.These findings suggest that the mutations in GBA,SNCA,and VPS35 are not likely to play an important role in the genetic susceptibility to AD in Chinese populations.The study was approved by the Ethics Committee of Xiangya Hospital,Central South University,China on March 9,2016(approval No.201603198).
基金Howard Lopes Ribeiro Junior is recipient of a CNPq Research Productivity Scholarship-Level 2(Project:Chamada CNPq N°09/2023-Bolsas de Produtividade em Pesquisa-PQ#305659/2023-5)funded by the Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnol ógico(FUNCAP)(UNI-0210-00007.01.00/23)entitled:“Estabelecimento de um Escore de Risco Poligênico(PRS)para a Neoplasia Mielodispl ásica no idoso:uma coorte Brasileira.
文摘Parkinson’s disease(PD)is a complex genetic neurodegenerative disorder.Epidemiology genetic discoveries have increased our understanding of the molecular contributors to Parkinson’s pathophysiology,especially when associated with the advent of genome-wide association studies(GWAS)technologies in the discovery of the risk linked to common germline genetic variants.The biggest limitation of those studies on genetic susceptibility to PD is the lack of information describing the impact of individuals’ancestry on risk associations,especially in non-European populations.Current genetic data are mainly based on individuals of European origin,particularly those included in the UK biobank project.The effects of these ethical discrepancies can directly impact the discovery of risk variants associated with PD susceptibility and clinical management of PD patients in admixture populations,for example.Thus,we performed a PROSPERO-registered systematic review to elucidate the current state of the art about the role of common genetic variants based on GWAS studies in advancing precision medicine for PD susceptibility and pathobiology in multiethnic and non-European populations.Also,we discuss whether there are similarities or discrepancies of these data in relation to genomic data obtained in studies with PD patients of European origin.
文摘Congenital heart disease(CHD)is observed in up to 1%of live births and is one of the leading causes of mortality from birth defects.While hundreds of genes have been implicated in the genetic etiology of CHD,their role in CHD pathogenesis is still poorly understood.This is largely a reflection of the sporadic nature of CHD,as well as its variable expressivity and incomplete penetrance.We reviewed the monogenic causes and evidence for oligogenic etiology of CHD,as well as the role of de novo mutations,common variants,and genetic modifiers.For further mechanistic insight,we leveraged single-cell data across species to investigate the cellular expression characteristics of genes implicated in CHD in developing human and mouse embryonic hearts.Understanding the genetic etiology of CHD may enable the application of precision medicine and prenatal diagnosis,thereby facilitating early intervention to improve outcomes for patients with CHD.
基金supported by CHINACANADA Joint Initiative on Alzheimer’s Disease and Related Disorders(81261120571)the National Basic Research Development Program(973 Program)of China(2011CB504104)+6 种基金Scientific Promoting Project of Beijing Institute for Brain Disorders(BIBDPXM2014_014226_000016)Seed Grant of International Alliance of Translational Neuroscience(PXM2014_014226_000006)Key Medical Professional Development Plan of Beijing Municipal Administration of Hospitals(ZYLX201301)the National Science and Technology Major Project for‘‘Major New Drug Innovation and Development’’of the Twelfth 5-year Plan Period of China(2011ZX09307-001-03)the Major Project of the Science and Technology Plan of the Beijing Municipal Science&Technology Commission of China(D111107003111009)the National Key Technology R&D Program in the Eleventh Five-year Plan Period of China(2006BAI02B01)the Key Project of the National Natural Science Foundation of China(30830045)
文摘Genome-wide association studies（GWASs）have revealed a plethora of putative susceptibility genes for Alzheimer＇s disease（AD）. With the sole exception of the APOE gene, these AD susceptibility genes have not been unequivocally validated in independent studies. No single novel functional risk genetic variant has been identified. In this review, we evaluate recent GWASs of AD, and discuss their significance, limitations, and challenges in the investigation of the genetic spectrum of AD.
文摘Glutamate receptors and schizophrenia:Schizophrenia is a chronic mental disorder affecting approximately 1%of the global population,with 70%-80%heritability.It has a multifactorial etiology involving both environmental factors and a complex polygenic genetic architecture.Over the last two decades,large-scale genome-wide approaches revealed contributions of common variants with individually small effect sizes and of rare copy number variants with a large effect size.N-methy l-D-a spar tat e receptor(NMDAR)hypofunction has been implicated as a central mechanism in the pathophysiology of schizophrenia(Coyle et al.,2020).
