目的对1例佩梅病家系蛋白脂质蛋白1(proteolipid protein 1,PLP1)基因新型突变进行遗传学分析。方法归纳整理1例佩梅病先证者及其家系成员的表征及基因分析结果。结果先证者为一胎男孩,出生后逐渐眼球震颤、走路不稳、发育迟缓,自诉多...目的对1例佩梅病家系蛋白脂质蛋白1(proteolipid protein 1,PLP1)基因新型突变进行遗传学分析。方法归纳整理1例佩梅病先证者及其家系成员的表征及基因分析结果。结果先证者为一胎男孩,出生后逐渐眼球震颤、走路不稳、发育迟缓,自诉多地诊治无效,头颅磁共振成像(magnetic resonance imaging,MRI)显示脑白质发育不佳,髓鞘形成不良,7岁时基因检测确诊为佩梅病,其父表型基因均正常,其母为表型正常的杂合子携带者;先证者母亲孕12周左右行胎儿绒毛检测确诊二胎为杂合变异,经遗传咨询后正常分娩一个表型正常的女孩;先证者母亲孕18周时羊水穿刺确诊三胎,与先证者突变位点一致,遗传方式评估后最终行引产终止妊娠。先证者家系半合子变异为新型突变,且通过美国医学遗传学与基因组学学会(American College of Medical Genetics and Genomics,ACMG)致病性分析证实为致病位点。由于该病的异质性和可变性,对其明确诊断至关重要。结论本研究报道了1例佩梅病家系PLP1基因的新型突变,扩大了PLP1基因致病图谱,为产前诊断提供了新的见解。展开更多
Plp1-lineage Schwann cells(SCs)of peripheral nerve play a critical role in vascular remodeling and osteogenic differentiation during the early stage of bone healing,and the abnormal plasticity of SCs would jeopardize ...Plp1-lineage Schwann cells(SCs)of peripheral nerve play a critical role in vascular remodeling and osteogenic differentiation during the early stage of bone healing,and the abnormal plasticity of SCs would jeopardize the bone regeneration.However,how Plp1-lineage cells respond to injury and initiate the vascularized osteogenesis remains incompletely understood.Here,by employing single-cell transcriptional profiling combined with lineage-specific tracing models,we uncover that Plp1-lineage cells undergoing injury-induced glia-to-MSCs transition contributed to osteogenesis and revascularization in the initial stage of bone injury.Importantly,our data demonstrated that the Sonic hedgehog(Shh)signaling was responsible for the transition process initiation,which was strongly activated by c-Jun/SIRT6/BAF170 complex-driven Shh enhancers.Collectively,these findings depict an injuryspecific niche signal-mediated Plp1-lineage cells transition towards Gli1+MSCs and may be instructive for approaches to promote bone regeneration during aging or other bone diseases.展开更多
PLP City Range项目坐落在曼谷通罗地区一个宁静的高档社区内,是一座为尖端高尔夫模拟中心建造的创新性混合用途建筑。引人注目的建筑立面,采用曲面预制混凝土板正反向拼贴组合而成,兼具美学和功能性。这些造型独特的混凝土模块在自然...PLP City Range项目坐落在曼谷通罗地区一个宁静的高档社区内,是一座为尖端高尔夫模拟中心建造的创新性混合用途建筑。引人注目的建筑立面,采用曲面预制混凝土板正反向拼贴组合而成,兼具美学和功能性。这些造型独特的混凝土模块在自然光下形成光影交织的效果,巧妙地呼应了高尔夫运动挥杆时的优雅弧线,在视觉上呈现这项运动独特的魅力。展开更多
文摘目的对1例佩梅病家系蛋白脂质蛋白1(proteolipid protein 1,PLP1)基因新型突变进行遗传学分析。方法归纳整理1例佩梅病先证者及其家系成员的表征及基因分析结果。结果先证者为一胎男孩,出生后逐渐眼球震颤、走路不稳、发育迟缓,自诉多地诊治无效,头颅磁共振成像(magnetic resonance imaging,MRI)显示脑白质发育不佳,髓鞘形成不良,7岁时基因检测确诊为佩梅病,其父表型基因均正常,其母为表型正常的杂合子携带者;先证者母亲孕12周左右行胎儿绒毛检测确诊二胎为杂合变异,经遗传咨询后正常分娩一个表型正常的女孩;先证者母亲孕18周时羊水穿刺确诊三胎,与先证者突变位点一致,遗传方式评估后最终行引产终止妊娠。先证者家系半合子变异为新型突变,且通过美国医学遗传学与基因组学学会(American College of Medical Genetics and Genomics,ACMG)致病性分析证实为致病位点。由于该病的异质性和可变性,对其明确诊断至关重要。结论本研究报道了1例佩梅病家系PLP1基因的新型突变,扩大了PLP1基因致病图谱,为产前诊断提供了新的见解。
基金supported by the National Natural Science Foundation of China(grants 81970910 and 82370931)Jiangsu Province Capability Improvement Project through Science,Technology and Education-Jiangsu Provincial Research Hospital Cultivation Unit(YJXYYJSDW4)Jiangsu Provincial Medical Innovation Center(CXZX202227).
文摘Plp1-lineage Schwann cells(SCs)of peripheral nerve play a critical role in vascular remodeling and osteogenic differentiation during the early stage of bone healing,and the abnormal plasticity of SCs would jeopardize the bone regeneration.However,how Plp1-lineage cells respond to injury and initiate the vascularized osteogenesis remains incompletely understood.Here,by employing single-cell transcriptional profiling combined with lineage-specific tracing models,we uncover that Plp1-lineage cells undergoing injury-induced glia-to-MSCs transition contributed to osteogenesis and revascularization in the initial stage of bone injury.Importantly,our data demonstrated that the Sonic hedgehog(Shh)signaling was responsible for the transition process initiation,which was strongly activated by c-Jun/SIRT6/BAF170 complex-driven Shh enhancers.Collectively,these findings depict an injuryspecific niche signal-mediated Plp1-lineage cells transition towards Gli1+MSCs and may be instructive for approaches to promote bone regeneration during aging or other bone diseases.
文摘PLP City Range项目坐落在曼谷通罗地区一个宁静的高档社区内,是一座为尖端高尔夫模拟中心建造的创新性混合用途建筑。引人注目的建筑立面,采用曲面预制混凝土板正反向拼贴组合而成,兼具美学和功能性。这些造型独特的混凝土模块在自然光下形成光影交织的效果,巧妙地呼应了高尔夫运动挥杆时的优雅弧线,在视觉上呈现这项运动独特的魅力。
