Purpose The present study aimed to evaluate the genetic diagnostic yield and accuracy of exome sequencing in Chinese patients with split hand–foot malformation(SHFM),a severe heterogeneous congenital anomaly characte...Purpose The present study aimed to evaluate the genetic diagnostic yield and accuracy of exome sequencing in Chinese patients with split hand–foot malformation(SHFM),a severe heterogeneous congenital anomaly characterized by hypodevelopment of the central ray of the hands and feet.Methods A cohort of seven families and five sporadic patients with SHFM was investigated.Genomic DNA was prepared from the peripheral blood of affected as well as unaffected individuals.Whole exome sequencing(WES)was performed to identify the pathogenic mutations.Array-based comparative genomic hybridization(aCGH),CytoScan,quantitative polymerase chain reaction(qPCR),and Sanger sequencing were performed to validate the findings of WES.WES data of an additional cohort of 24 patients with non-SHFM congenital hand anomalies were analyzed as the control.Results Pathogenic variants of TP63,c.G956A p.R319H,and c.T602A:p.L201H,were identified in two families by WES.In the remaining patients,copy number analysis of the WES data by XHMM software identified pathogenic 10q 24 duplication in five individuals from three families,which was further validated via CytoScan and qPCR;however,WES could not detect duplication in 10q24 in an additional cohort of 24 individuals with non-SHFM congenital hand anomaly.Importantly,qPCR analysis of the 10q24 region copy number revealed a definite consistency with WES data in all individuals.Genotype–phenotype analysis did not present any unique feature that could differentiate between the families with TP63 mutation and 10q24 duplication.Conclusions Our study demonstrated that WES is an accurate and sensitive method to detect the pathogenic 10q24 duplication.Collectively,with TP63 mutation,a single WES testing could yield a diagnosis rate of about 40%(5/12)for the SHFM patients,at least in our cohort.As the genotype–phenotype correlation remains unclear,WES could be used as a cost-effective method for the genetic diagnosis of SHFM.展开更多
According to clinical studies,upper limb robotic suits are vital to reduce therapist fatigue and accelerate patient rehabilitation.Soft pneumatic actuators have drawn increasing attention for the development of wearab...According to clinical studies,upper limb robotic suits are vital to reduce therapist fatigue and accelerate patient rehabilitation.Soft pneumatic actuators have drawn increasing attention for the development of wearable robots due to their low weight,flexibility,and high power-to-weight ratio.However,most of current actuators were designed for the flexion assistance of a specific joint,and that for joint extension requires further investigation.Furthermore,designing an actuator for diverse working scenarios remains a challenge.In this paper,we propose an all-fabric bi-directional actuator to assist the flexion and extension of the elbow,wrist,and fingers.A mathematical model is presented that predicts the deformation and guides the design of the proposed bi-directional actuator.To further validate the applicability and adaptability of the proposed actuator for different joints,we developed a 3-DOF soft robotic suit.Preliminary results show that the robotic suit can assist the motion of the elbow,wrist,and finger of the subject.展开更多
基金We would like to thank the families for their participation in this study.We would also like to thank our funding sources:This study was supported by National Science Funding of China No.81772115 and 81571930 to BW.
文摘Purpose The present study aimed to evaluate the genetic diagnostic yield and accuracy of exome sequencing in Chinese patients with split hand–foot malformation(SHFM),a severe heterogeneous congenital anomaly characterized by hypodevelopment of the central ray of the hands and feet.Methods A cohort of seven families and five sporadic patients with SHFM was investigated.Genomic DNA was prepared from the peripheral blood of affected as well as unaffected individuals.Whole exome sequencing(WES)was performed to identify the pathogenic mutations.Array-based comparative genomic hybridization(aCGH),CytoScan,quantitative polymerase chain reaction(qPCR),and Sanger sequencing were performed to validate the findings of WES.WES data of an additional cohort of 24 patients with non-SHFM congenital hand anomalies were analyzed as the control.Results Pathogenic variants of TP63,c.G956A p.R319H,and c.T602A:p.L201H,were identified in two families by WES.In the remaining patients,copy number analysis of the WES data by XHMM software identified pathogenic 10q 24 duplication in five individuals from three families,which was further validated via CytoScan and qPCR;however,WES could not detect duplication in 10q24 in an additional cohort of 24 individuals with non-SHFM congenital hand anomaly.Importantly,qPCR analysis of the 10q24 region copy number revealed a definite consistency with WES data in all individuals.Genotype–phenotype analysis did not present any unique feature that could differentiate between the families with TP63 mutation and 10q24 duplication.Conclusions Our study demonstrated that WES is an accurate and sensitive method to detect the pathogenic 10q24 duplication.Collectively,with TP63 mutation,a single WES testing could yield a diagnosis rate of about 40%(5/12)for the SHFM patients,at least in our cohort.As the genotype–phenotype correlation remains unclear,WES could be used as a cost-effective method for the genetic diagnosis of SHFM.
基金The research is supported by the National Natural Science Foundation of China(52275002)the Open Laboratory Concept Verification Project of Zhongguancun National Demonstration Zone(Grant No.202005226).
文摘According to clinical studies,upper limb robotic suits are vital to reduce therapist fatigue and accelerate patient rehabilitation.Soft pneumatic actuators have drawn increasing attention for the development of wearable robots due to their low weight,flexibility,and high power-to-weight ratio.However,most of current actuators were designed for the flexion assistance of a specific joint,and that for joint extension requires further investigation.Furthermore,designing an actuator for diverse working scenarios remains a challenge.In this paper,we propose an all-fabric bi-directional actuator to assist the flexion and extension of the elbow,wrist,and fingers.A mathematical model is presented that predicts the deformation and guides the design of the proposed bi-directional actuator.To further validate the applicability and adaptability of the proposed actuator for different joints,we developed a 3-DOF soft robotic suit.Preliminary results show that the robotic suit can assist the motion of the elbow,wrist,and finger of the subject.
