Clubfoot,medically termed congenital talipes equinovarus(CTEV),is a prevalent musculoskeletal birth defect,affecting approximately 0.3%of all live births.This serious congenital anomaly results from structural abnorma...Clubfoot,medically termed congenital talipes equinovarus(CTEV),is a prevalent musculoskeletal birth defect,affecting approximately 0.3%of all live births.This serious congenital anomaly results from structural abnormalities in the foot and lower leg,leading to abnormal positioning of the ankle and foot joints.This review provides a comprehensive overview of the causative factors associated with CTEV and evaluates current therapeutic approaches.Although variations in genes encoding contractile proteins of skeletal myofibers have been proposed as contributors to the etiology of CTEV,no definitive candidate genes have been conclusively linked to increased risk.However,genes such as TBX4,PITX1,and members of the HOXA,HOXC,and HOXD clusters,as well as NAT2,have been implicated in the condition’s development,playing critical roles in limb development,muscle formation,and tissue differentiation.Also,Axin1 plays a key role in joint formation and skeletal development by inhibiting β-catenin-BMP signaling.It could significantly serve as a therapeutic target for fibular hemimelia and multiple synostoses syndrome.The exact mechanisms and the extent of their physical and genetic interactions remain subjects of ongoing research.Understanding the genetic determinants and cellular pathways involved in CTEV is crucial for unravelling the pathophysiology of this complex deformity.展开更多
Menopause is a biological event associated with the complete cessation of a woman’s reproductive ability.Early menopause is defined as entry into menopause between the ages of 40 and 45 years,and has a significant im...Menopause is a biological event associated with the complete cessation of a woman’s reproductive ability.Early menopause is defined as entry into menopause between the ages of 40 and 45 years,and has a significant impact on the fertility of affected women.Early menopause is a complex and heterogeneous disorder that is influenced by multiple genetic and environmental factors,as well as the interactions between these factors.Genome-wide association study(GWAS)is a novel strategy that has recently come into use as a way to overcome the limitations of genome-wide linkage analyses and candidate gene association approaches to discover novel susceptibility loci for early menopause.GWAS has identified many new candidate genes or loci associated with early menopause.In this review,we provide an overview of the current understanding of the genetic factors associated with early menopause that have been identified by GWAS.We also discuss potential approaches that could be used in the future to identify new genes associated with early menopause.展开更多
基金supported by the National Key Research and Development Program of China(No.2022YFA1207500)the National Natural Science Foundation of China(No.82394445,82161160342,82030067 to D.C.)the Shenzhen Science and Technology Innovation Bureau(Guangdong,China)(No.LCYSSQ20220823091402005-E-001)to D.C.
文摘Clubfoot,medically termed congenital talipes equinovarus(CTEV),is a prevalent musculoskeletal birth defect,affecting approximately 0.3%of all live births.This serious congenital anomaly results from structural abnormalities in the foot and lower leg,leading to abnormal positioning of the ankle and foot joints.This review provides a comprehensive overview of the causative factors associated with CTEV and evaluates current therapeutic approaches.Although variations in genes encoding contractile proteins of skeletal myofibers have been proposed as contributors to the etiology of CTEV,no definitive candidate genes have been conclusively linked to increased risk.However,genes such as TBX4,PITX1,and members of the HOXA,HOXC,and HOXD clusters,as well as NAT2,have been implicated in the condition’s development,playing critical roles in limb development,muscle formation,and tissue differentiation.Also,Axin1 plays a key role in joint formation and skeletal development by inhibiting β-catenin-BMP signaling.It could significantly serve as a therapeutic target for fibular hemimelia and multiple synostoses syndrome.The exact mechanisms and the extent of their physical and genetic interactions remain subjects of ongoing research.Understanding the genetic determinants and cellular pathways involved in CTEV is crucial for unravelling the pathophysiology of this complex deformity.
基金supported by the grants from the National Key Research and Development Program of China(2016YFC1000500)the National Natural Science Foundation of China(81430005,31521003)the Commission for Science and Technology of Shanghai Municipality(13JC1407600)
文摘Menopause is a biological event associated with the complete cessation of a woman’s reproductive ability.Early menopause is defined as entry into menopause between the ages of 40 and 45 years,and has a significant impact on the fertility of affected women.Early menopause is a complex and heterogeneous disorder that is influenced by multiple genetic and environmental factors,as well as the interactions between these factors.Genome-wide association study(GWAS)is a novel strategy that has recently come into use as a way to overcome the limitations of genome-wide linkage analyses and candidate gene association approaches to discover novel susceptibility loci for early menopause.GWAS has identified many new candidate genes or loci associated with early menopause.In this review,we provide an overview of the current understanding of the genetic factors associated with early menopause that have been identified by GWAS.We also discuss potential approaches that could be used in the future to identify new genes associated with early menopause.
