舞蹈病-棘红细胞增多症(chorea-acanthocytosis,ChAc)是一种罕见的常染色体隐性遗传病,其临床特征较为复杂,可累及运动、神经、精神及内分泌等多个系统,常伴有头颈部不自主运动、进行性舞蹈样运动障碍、认知能力下降等临床表现,极易与...舞蹈病-棘红细胞增多症(chorea-acanthocytosis,ChAc)是一种罕见的常染色体隐性遗传病,其临床特征较为复杂,可累及运动、神经、精神及内分泌等多个系统,常伴有头颈部不自主运动、进行性舞蹈样运动障碍、认知能力下降等临床表现,极易与麦克劳德综合征、类亨廷顿病2型、泛酸激酶相关的神经退行性等疾病相混淆[1];液泡蛋白分类同源物13A(vacuolar protein sorting homolog 13A,VPS13A)基因编码蛋白chorein对于维持细胞膜正常结构及神经元细胞功能具有重要作用,其突变与CHAc发病相关。现将南昌大学第一附属医院诊治的1例VPS13A基因双位点纯合突变致ChAc患者报告如下。展开更多
BACKGROUND Autosomal recessive spinocerebellar ataxia type 4(SCAR4)is a type of SCA that is a group of hereditary diseases characterized by gait ataxia.The main clinical features of SCAR4 are progressive cerebellar at...BACKGROUND Autosomal recessive spinocerebellar ataxia type 4(SCAR4)is a type of SCA that is a group of hereditary diseases characterized by gait ataxia.The main clinical features of SCAR4 are progressive cerebellar ataxia,pyramidal signs,neuropathy,and macrosaccadic intrusions.To date,many gene dysfunctions have been reported to be associated with SCAR4.CASE SUMMARY Here,we report a novel compound heterozygous mutation,c.3288delA(p.Asp1097-ThrfsTer6),in the VPS13D gene in a young female Chinese patient.The patient found something wrong with her legs about 10 years ago and presented with the typical characteristics of SCAR4 when she came to the hospital,including ataxia,neuropathy,and positive pyramidal signs.She was then diagnosed with SCAR4 and went home with symptomatic schemes.CONCLUSION SCAR4 is a hereditary disease characterized by ataxia,pyramidal signs,neuropathy,and macrosaccadic intrusions.We report a novel compound heterozygous mutation,c.3288delA(p.Asp1097ThrfsTer6),in the VPS13D gene,which enriches the gene mutation spectrum and provides additional information about SCAR4.展开更多
Abnormal mitochondrial dynamics can lead to seizures,and improved mitochon-drial dynamics can alleviate seizures.Vacuolar protein sorting 13D(VPS13D)is closely associ-ated with regulating mitochondrial homeostasis and...Abnormal mitochondrial dynamics can lead to seizures,and improved mitochon-drial dynamics can alleviate seizures.Vacuolar protein sorting 13D(VPS13D)is closely associ-ated with regulating mitochondrial homeostasis and autophagy.However,further investigation is required to determine whether VPS13D affects seizures by influencing mitochondrial dy-namics and autophagy.We aimed to investigate the influence of VPS13D on behavior in a rat model of acute epileptic seizures.Hence,we established an acute epileptic seizure rat model and employed the CRISPR/CAS9 technology to construct a lentivirus to silence the Vps13d gene.Furthermore,we used the HT22 mouse hippocampal neuron cell line to establish a stable strain with suppressed expression of Vps13d in vitro.Then,we performed quantitative prote-omic and bioinformatics analyses to confirm the mechanism by which VPS13D influences mito-chondrial dynamics and autophagy,both in vitro and in vivo using the experimental acute epileptic seizure model.We found that knockdown of Vps13d resulted in reduced seizure la-tency and increased seizure frequency in the experimental rats.Immunofluorescence staining and western blot analysis revealed a significant increase in mitochondrial dynamin-related pro-tein 1 expression following Vps13d knockdown.Moreover,we observed a significant reduction in LC3Il protein expression levels and the LC31/LC3l ratio(indicators for autophagy)accompa-nied by a significant increase in P62 expression(an autophagy adaptor protein).The proteomic analysis confirmed the up-regulation of P62 protein expression.Therefore,we propose that VPS13D plays a role in modulating seizures by influencing mitochondrial dynamics and autophagy.展开更多
We present the case of a novel homozygous nonsense(c.4846C>T[p.R1616X])mutation in the VPS13B in a Chinese boy with the primary symptoms of Cohen syndrome.This case presented with manifestations consistent with Coh...We present the case of a novel homozygous nonsense(c.4846C>T[p.R1616X])mutation in the VPS13B in a Chinese boy with the primary symptoms of Cohen syndrome.This case presented with manifestations consistent with Cohen syndrome,including developmental delay,microcephaly,typical facial features,short stature,muscle hypotonia,neutropenia,and abnormal dental development;however,the patient did not have the typical findings of obesity,myopia,progressive retinal dystrophy,or epilepsy.The patient had a homozygous nonsense mutation(NM_017890:c.4846C>T[p.R1616X]).His brother,sister,and parents are heterozygous for the mutation.This locus variation has not been previously reported in Chinese children.Different mutation sites have different phenotypes.Cohen syndrome caused by a homozygous nonsense mutation of the VPS13B c.4846C>T(p.R1616X)does not present with obesity,ophthalmic abnormalities,or epilepsy,but has abnormal dental development.This may be related to the premature termination of peptide synthesis caused by nonsense mutations at this site.展开更多
文摘舞蹈病-棘红细胞增多症(chorea-acanthocytosis,ChAc)是一种罕见的常染色体隐性遗传病,其临床特征较为复杂,可累及运动、神经、精神及内分泌等多个系统,常伴有头颈部不自主运动、进行性舞蹈样运动障碍、认知能力下降等临床表现,极易与麦克劳德综合征、类亨廷顿病2型、泛酸激酶相关的神经退行性等疾病相混淆[1];液泡蛋白分类同源物13A(vacuolar protein sorting homolog 13A,VPS13A)基因编码蛋白chorein对于维持细胞膜正常结构及神经元细胞功能具有重要作用,其突变与CHAc发病相关。现将南昌大学第一附属医院诊治的1例VPS13A基因双位点纯合突变致ChAc患者报告如下。
文摘BACKGROUND Autosomal recessive spinocerebellar ataxia type 4(SCAR4)is a type of SCA that is a group of hereditary diseases characterized by gait ataxia.The main clinical features of SCAR4 are progressive cerebellar ataxia,pyramidal signs,neuropathy,and macrosaccadic intrusions.To date,many gene dysfunctions have been reported to be associated with SCAR4.CASE SUMMARY Here,we report a novel compound heterozygous mutation,c.3288delA(p.Asp1097-ThrfsTer6),in the VPS13D gene in a young female Chinese patient.The patient found something wrong with her legs about 10 years ago and presented with the typical characteristics of SCAR4 when she came to the hospital,including ataxia,neuropathy,and positive pyramidal signs.She was then diagnosed with SCAR4 and went home with symptomatic schemes.CONCLUSION SCAR4 is a hereditary disease characterized by ataxia,pyramidal signs,neuropathy,and macrosaccadic intrusions.We report a novel compound heterozygous mutation,c.3288delA(p.Asp1097ThrfsTer6),in the VPS13D gene,which enriches the gene mutation spectrum and provides additional information about SCAR4.
基金supported by the Science and Technology Fund Project of the Guizhou Provincial Health Commission (China) (No.gzwkj2023-109,gzwkj2021.017,gzwjkj2020-1-010)the Science and Technology Plan Project of Zunyi City,Guizhou,China (No.ZSKHZC-HZ (2020)172)+1 种基金the Science and Technology Project in Guizhou Province,China (No.QKHJC-ZK[2021]NO.408)the National Natural Science Foundation of China (No.82101527).
文摘Abnormal mitochondrial dynamics can lead to seizures,and improved mitochon-drial dynamics can alleviate seizures.Vacuolar protein sorting 13D(VPS13D)is closely associ-ated with regulating mitochondrial homeostasis and autophagy.However,further investigation is required to determine whether VPS13D affects seizures by influencing mitochondrial dy-namics and autophagy.We aimed to investigate the influence of VPS13D on behavior in a rat model of acute epileptic seizures.Hence,we established an acute epileptic seizure rat model and employed the CRISPR/CAS9 technology to construct a lentivirus to silence the Vps13d gene.Furthermore,we used the HT22 mouse hippocampal neuron cell line to establish a stable strain with suppressed expression of Vps13d in vitro.Then,we performed quantitative prote-omic and bioinformatics analyses to confirm the mechanism by which VPS13D influences mito-chondrial dynamics and autophagy,both in vitro and in vivo using the experimental acute epileptic seizure model.We found that knockdown of Vps13d resulted in reduced seizure la-tency and increased seizure frequency in the experimental rats.Immunofluorescence staining and western blot analysis revealed a significant increase in mitochondrial dynamin-related pro-tein 1 expression following Vps13d knockdown.Moreover,we observed a significant reduction in LC3Il protein expression levels and the LC31/LC3l ratio(indicators for autophagy)accompa-nied by a significant increase in P62 expression(an autophagy adaptor protein).The proteomic analysis confirmed the up-regulation of P62 protein expression.Therefore,we propose that VPS13D plays a role in modulating seizures by influencing mitochondrial dynamics and autophagy.
文摘We present the case of a novel homozygous nonsense(c.4846C>T[p.R1616X])mutation in the VPS13B in a Chinese boy with the primary symptoms of Cohen syndrome.This case presented with manifestations consistent with Cohen syndrome,including developmental delay,microcephaly,typical facial features,short stature,muscle hypotonia,neutropenia,and abnormal dental development;however,the patient did not have the typical findings of obesity,myopia,progressive retinal dystrophy,or epilepsy.The patient had a homozygous nonsense mutation(NM_017890:c.4846C>T[p.R1616X]).His brother,sister,and parents are heterozygous for the mutation.This locus variation has not been previously reported in Chinese children.Different mutation sites have different phenotypes.Cohen syndrome caused by a homozygous nonsense mutation of the VPS13B c.4846C>T(p.R1616X)does not present with obesity,ophthalmic abnormalities,or epilepsy,but has abnormal dental development.This may be related to the premature termination of peptide synthesis caused by nonsense mutations at this site.
