Background： Progressive myoclonus epilepsies （PMEs） conaprise a group of rare genetic disorders characterized by action rnyoclonus, epileptic seizures, and ataxia with progressive neurologic decline. Due to clinica...Background： Progressive myoclonus epilepsies （PMEs） conaprise a group of rare genetic disorders characterized by action rnyoclonus, epileptic seizures, and ataxia with progressive neurologic decline. Due to clinical and genetic heterogeneity of PMEs, it is difficult to decide which genes are affected. The aim of this study was to report an action myoclonus with or without renal failure syndrome （EPM4） fhmily and summarize the clinical and genetic characteristics of all reported EPM4 patients. Meihods： In the present study, targeted next-generation sequencing （NGS） was applied to screen causative genes in a Chinese PME family. The candidaie variant was further confirmed by cosegregation analysis and further functional analysis, including the reverse transcription polymerase chain reaction and Western blot of the proband＇s muscle. Moreovel, literature data on the clinical and mutational features of all reported EPM4 patients were reviewed. Results： The gene analysis revealed a novel homozygous splicing mutation （c.995-1G〉A） of the SCARB2 gene in two brothers. Further functional analysis revealed that this mutation led to loss function of the SCARB2 protein. The classification of the candidate variant, according to the American College of Medical Genetics and Genomics standards and guidelines and functional analysis, was pathogenic. Therefore, these two brothers were finally diagnostically confirmed as EPM4. Conclusions： These present results suggest the potential for targeted NGS to conduct a more rapid and precise diagnosis for PME patients. A literature review revealed that mutations in the different functional domains of SCARB2 appear to be associated with the phenotype of EPM4.展开更多
To the Editor:Spinal muscular atrophy(SMA)is an autosomal recessive disease caused by a deficiency of the survival motor neuron 1(SMN1)protein,which causes the loss of motor neurons in the anterior horn of the spinal ...To the Editor:Spinal muscular atrophy(SMA)is an autosomal recessive disease caused by a deficiency of the survival motor neuron 1(SMN1)protein,which causes the loss of motor neurons in the anterior horn of the spinal cord.⑴A genetically similar gene,SMN2,has a translationally silent C-to-T transition at Position 6 in its 7th exon that causes only 10%correctly spliced full-length and functional SMN protein via alternative splicing.展开更多
China Jinping Underground Laboratory(CJPL)is ideal for studying solar,geo-,and supernova neutrinos.A precise measurement of the cosmic-ray background is essential in proceeding with R&D research for these MeV-scal...China Jinping Underground Laboratory(CJPL)is ideal for studying solar,geo-,and supernova neutrinos.A precise measurement of the cosmic-ray background is essential in proceeding with R&D research for these MeV-scale neutrino experiments.Using a 1-ton prototype detector for the Jinping Neutrino Experiment(JNE),we detected 264 high-energy muon events from a 645.2-day dataset from the first phase of CJPL(CJPL-I),reconstructed their directions,and measured the cosmic-ray muon flux to be (3.53±0.22_stat.±0.07_sys.)×-10^(-10)cm^(-2).The observed angular distributions indicate the leakage of cosmic-ray muon background and agree with simulation data accounting for Jinping mountain's terrain.A survey of muon fluxes at different laboratory locations,considering both those situated under mountains and those down mine shafts,indicates that the flux at the former is generally a factor of (4±2) larger than at the latter,with the same vertical overburden.This study provides a convenient back-of-the-envelope estimation for the muon flux of an underground experiment.展开更多
基金This work was supported by the grants from the National Natural Science Foundation of China （No. U1505222, No, 81322017, No. 81500980, and No. 81571100） and the National Key Clinical Specialty Discipline Construction Program and Key Clinical Specialty Discipline Construction Program of Fujian.
文摘Background： Progressive myoclonus epilepsies （PMEs） conaprise a group of rare genetic disorders characterized by action rnyoclonus, epileptic seizures, and ataxia with progressive neurologic decline. Due to clinical and genetic heterogeneity of PMEs, it is difficult to decide which genes are affected. The aim of this study was to report an action myoclonus with or without renal failure syndrome （EPM4） fhmily and summarize the clinical and genetic characteristics of all reported EPM4 patients. Meihods： In the present study, targeted next-generation sequencing （NGS） was applied to screen causative genes in a Chinese PME family. The candidaie variant was further confirmed by cosegregation analysis and further functional analysis, including the reverse transcription polymerase chain reaction and Western blot of the proband＇s muscle. Moreovel, literature data on the clinical and mutational features of all reported EPM4 patients were reviewed. Results： The gene analysis revealed a novel homozygous splicing mutation （c.995-1G〉A） of the SCARB2 gene in two brothers. Further functional analysis revealed that this mutation led to loss function of the SCARB2 protein. The classification of the candidate variant, according to the American College of Medical Genetics and Genomics standards and guidelines and functional analysis, was pathogenic. Therefore, these two brothers were finally diagnostically confirmed as EPM4. Conclusions： These present results suggest the potential for targeted NGS to conduct a more rapid and precise diagnosis for PME patients. A literature review revealed that mutations in the different functional domains of SCARB2 appear to be associated with the phenotype of EPM4.
基金grants from the National Natural Science Foundation of China(Nos.81771230,U1905210)the Joint Funds for the Innovation of Science and Technology of Fujian Province(Nos.2017Y9094 and 2018Y9082)the National Key Clinical Specialty Discipline Construction Program,the Key Clinical Specialty Discipline Construction Program of Fujian,and the Startup Fund for Scientific Research of Fujian Medical University(Nos.2018QH1050 and 2018QH2035).
文摘To the Editor:Spinal muscular atrophy(SMA)is an autosomal recessive disease caused by a deficiency of the survival motor neuron 1(SMN1)protein,which causes the loss of motor neurons in the anterior horn of the spinal cord.⑴A genetically similar gene,SMN2,has a translationally silent C-to-T transition at Position 6 in its 7th exon that causes only 10%correctly spliced full-length and functional SMN protein via alternative splicing.
基金Supported in part by the National Natural Science Foundation of China(11620101004,11475093)the Key Laboratory of Particle&Radiation Imaging(Tsinghua University,the CAS Center for Excellence in Particle Physics(CCEPP),and Guangdong Basic and Applied Basic Research Foundation(2019A1515012216)Portion of this work performed at Brookhaven National Laboratory is supponted in part by the United States Department of Energy(DE-SC0012704)。
文摘China Jinping Underground Laboratory(CJPL)is ideal for studying solar,geo-,and supernova neutrinos.A precise measurement of the cosmic-ray background is essential in proceeding with R&D research for these MeV-scale neutrino experiments.Using a 1-ton prototype detector for the Jinping Neutrino Experiment(JNE),we detected 264 high-energy muon events from a 645.2-day dataset from the first phase of CJPL(CJPL-I),reconstructed their directions,and measured the cosmic-ray muon flux to be (3.53±0.22_stat.±0.07_sys.)×-10^(-10)cm^(-2).The observed angular distributions indicate the leakage of cosmic-ray muon background and agree with simulation data accounting for Jinping mountain's terrain.A survey of muon fluxes at different laboratory locations,considering both those situated under mountains and those down mine shafts,indicates that the flux at the former is generally a factor of (4±2) larger than at the latter,with the same vertical overburden.This study provides a convenient back-of-the-envelope estimation for the muon flux of an underground experiment.
