目的:观察遗传性压迫易感性神经病(hereditary neuropathy with liability to pressure palsies,HNPP)的临床、电生理、病理及遗传学特点,以提高对本病的认识及诊断水平。方法:对5例HNPP患者进行详尽的临床检查、神经电生理、腓肠神经活...目的:观察遗传性压迫易感性神经病(hereditary neuropathy with liability to pressure palsies,HNPP)的临床、电生理、病理及遗传学特点,以提高对本病的认识及诊断水平。方法:对5例HNPP患者进行详尽的临床检查、神经电生理、腓肠神经活检,用多聚酶链反应(PCR)结合酶切方法检测HNPP患者17p11.2的基因缺失。结果:本组有3例来自同一家系,符合常染色体显性遗传模式,另2例为散发。多在20岁前起病,表现为复发性、无痛性、局灶性单神经病或多神经病,多于数天或数月内自行恢复,少数可遗留部分神经功能缺损。神经电生理检查有广泛性运动和感觉神经传导速度减慢,于易嵌压部位传导速度减慢更明显,并有远端运动潜伏期延迟。腓肠神经活检显示部分有髓神经纤维明显增粗,电镜可见有髓纤维髓鞘增厚,髓鞘板层层数增加。基因检测发现有3例存在17p11.2区包含PMP22基因在内的1.5Mb片段的缺失突变。结论:HNPP是一种常染色体显性遗传病,但也有散发,多于儿童期或青少年起病,表现为外伤或受压后反复出现肢体麻木、无力;生理的特点为广泛性神经传导速度减慢及远端运动潜伏期延迟;肌电图是诊断HNPP的重要筛选方法,有利于发现更多的病例;病理学特征是髓鞘增粗或典型的腊肠样结构;7p11.2区包含PMP22基因在内的1.5Mb片段的缺失突变是HNPP国人最常见的基因型,重组热点多位于REP的3.2kb区域内。展开更多
遗传性压力易感性周围神经病（Hereditary neuropathy with liability to pressure palsies,HNPP）是由人类周围髓鞘蛋白22（peripheral myelin protein 22,PMP22）基因缺失突变或点突变引起的一种少见的常染色体显性遗传性周围神经病。...遗传性压力易感性周围神经病（Hereditary neuropathy with liability to pressure palsies,HNPP）是由人类周围髓鞘蛋白22（peripheral myelin protein 22,PMP22）基因缺失突变或点突变引起的一种少见的常染色体显性遗传性周围神经病。HNPP多于20～30岁起病,以易卡压部位神经受到轻微牵拉或压迫后反复出现受累神经支配区域的麻木和无力为主要临床特征。展开更多
Objective: To describe a large family with hereditary neuropathy with liability to pressure palsies associated with central nervous system demyelination. Design: We examined the 18 members of a pedigree. Genetic analy...Objective: To describe a large family with hereditary neuropathy with liability to pressure palsies associated with central nervous system demyelination. Design: We examined the 18 members of a pedigree. Genetic analysis was performed on 15 subjects, standard nerve conduction studies on 10 subjects, and brain magnetic resonance imaging studies on 8 subjects. Results: Hereditary neuropathy with liability to pressure palsies was confirmed in 9 patients of the pedigree. Brain magnetic resonance imaging findings showed multiple areas of demyelination in 6 of 6 affected members and were normal in 2 of 2 healthy relatives. Magnetic resonance imaging abnormalities were predominantly located in the subcortical frontal white matter. All patients had acute and recurrent nerve palsies, while clinical features of central nervous system involvement were not a characteristic of this pedigree. Conclusions: We demonstrate that this association, previously reported in sporadic cases, is not coincidental. Therefore, patients with hereditary neuropathy with liability to pressure palsies can present central nervous system white matter lesions, and the role of the PMP22 (peripheral myelin protein 22) gene deletion in the central nervous system should be further studied.展开更多
目的:遗传性压力易感性周围神经病(hereditary neuropathy with liability to pressure palsy,HNPP)是一种少见的常染色体显性遗传周围神经病,通常由周围髓鞘蛋白22(peripheral myelin protein 22,PMP22)基因杂合缺失突变引起。本研究...目的:遗传性压力易感性周围神经病(hereditary neuropathy with liability to pressure palsy,HNPP)是一种少见的常染色体显性遗传周围神经病,通常由周围髓鞘蛋白22(peripheral myelin protein 22,PMP22)基因杂合缺失突变引起。本研究旨在探讨HNPP患者的临床和分子遗传学特征。方法:纳入2009至2023年就诊于中南大学湘雅三医院神经内科的HNPP患者,收集并分析患者的一般临床资料、神经电生理和分子遗传学检查结果。分子遗传学检查为提取外周血基因组DNA后采用多重连接探针扩增技术(multiplex ligation-dependent probe amplification,MLPA)进行PMP22大片段缺失的筛查;若未检测到PMP22缺失突变,则用二代测序法筛查PMP22点突变。进一步对HNPP相关文献进行回顾,分析HNPP患者的临床和分子遗传学特征。结果:共纳入来自24个无血缘关系的中国汉族家系的34例HNPP患者,包括25名男性和9名女性,平均22.0岁起病,有阳性家族史的家系占62.5%。30例患者出现周围神经麻痹的症状,常表现为发作性单肢无力伴/或麻木(25/30),亦可表现为发作性单侧喉返神经(迷走神经)麻痹(2/30)。体格检查可发现受累神经相应支配区域的肌肉无力(23/29)和浅感觉减退(9/29),踝反射减弱或消失(20/29),肢体远端肌肉萎缩(8/29)及高弓足(5/29)。多数患者(26/30)在急性发作后可完全恢复正常。有31例患者完成神经电生理检查,均表现为多发性周围神经损害,以运动及感觉神经髓鞘损害为主,多数患者可有远端运动潜伏期(distal motor latency,DML)明显延长,轻至中度的神经传导速度减慢,复合肌肉动作电位(compound muscle action potential,CMAP)及感觉神经动作电位(sensory nerve action potential,SNAP)波幅降低,有时可出现传导阻滞。正中神经运动传导速度为(48.5±5.5)m/s,CMAP波幅为(8.4±5.1)mV;正中神经感觉传导速度为(37.4±10.5)m/s,SNAP波幅为(14.4±13.0)μV。在24个HNPP家系中,经MLPA检测证实有23个家系为PMP22杂合缺失突变导致,经二代测序证实剩余1个家系为PMP22 c.434delT突变所致。文献检索到1734个进行了基因检测的HNPP确诊家系,其基因检测结果再次证实了PMP22杂合缺失突变是最常见的突变类型,占93.4%,其余突变类型包括PMP22微小突变(4.0%)、PMP22杂合不完全缺失突变(0.6%)、PMP22复杂易位突变(0.1%)。目前HNPP相关的PMP22微小突变共报道38种,包括错义突变(10/38)、无义突变(4/38)、碱基缺失突变(13/38)、碱基插入突变(3/38)、剪切位点突变(8/38)。HNPP患者最常表现为发作性无痛性单神经麻痹,腓总神经、尺神经和臂丛神经受累最为常见,约占75%。颅神经受累的患者仅有18例报道。结论:PMP22杂合缺失突变是HNPP最常见的突变类型。HNPP以发作性无痛性单神经麻痹为主要特点,主要累及腓总神经、尺神经等周围神经。神经电生理检查对于诊断本病具有较高的灵敏度和特异度,表现为广泛的脱髓鞘改变。对于怀疑HNPP的患者,首选完善神经电生理检查及PMP22大片段杂合缺失的检测。必要时可以完善Sanger测序或二代测序,对PMP22其他突变类型进行检测以防漏诊。展开更多
文摘目的:观察遗传性压迫易感性神经病(hereditary neuropathy with liability to pressure palsies,HNPP)的临床、电生理、病理及遗传学特点,以提高对本病的认识及诊断水平。方法:对5例HNPP患者进行详尽的临床检查、神经电生理、腓肠神经活检,用多聚酶链反应(PCR)结合酶切方法检测HNPP患者17p11.2的基因缺失。结果:本组有3例来自同一家系,符合常染色体显性遗传模式,另2例为散发。多在20岁前起病,表现为复发性、无痛性、局灶性单神经病或多神经病,多于数天或数月内自行恢复,少数可遗留部分神经功能缺损。神经电生理检查有广泛性运动和感觉神经传导速度减慢,于易嵌压部位传导速度减慢更明显,并有远端运动潜伏期延迟。腓肠神经活检显示部分有髓神经纤维明显增粗,电镜可见有髓纤维髓鞘增厚,髓鞘板层层数增加。基因检测发现有3例存在17p11.2区包含PMP22基因在内的1.5Mb片段的缺失突变。结论:HNPP是一种常染色体显性遗传病,但也有散发,多于儿童期或青少年起病,表现为外伤或受压后反复出现肢体麻木、无力;生理的特点为广泛性神经传导速度减慢及远端运动潜伏期延迟;肌电图是诊断HNPP的重要筛选方法,有利于发现更多的病例;病理学特征是髓鞘增粗或典型的腊肠样结构;7p11.2区包含PMP22基因在内的1.5Mb片段的缺失突变是HNPP国人最常见的基因型,重组热点多位于REP的3.2kb区域内。
文摘遗传性压力易感性周围神经病（Hereditary neuropathy with liability to pressure palsies,HNPP）是由人类周围髓鞘蛋白22（peripheral myelin protein 22,PMP22）基因缺失突变或点突变引起的一种少见的常染色体显性遗传性周围神经病。HNPP多于20～30岁起病,以易卡压部位神经受到轻微牵拉或压迫后反复出现受累神经支配区域的麻木和无力为主要临床特征。
文摘Objective: To describe a large family with hereditary neuropathy with liability to pressure palsies associated with central nervous system demyelination. Design: We examined the 18 members of a pedigree. Genetic analysis was performed on 15 subjects, standard nerve conduction studies on 10 subjects, and brain magnetic resonance imaging studies on 8 subjects. Results: Hereditary neuropathy with liability to pressure palsies was confirmed in 9 patients of the pedigree. Brain magnetic resonance imaging findings showed multiple areas of demyelination in 6 of 6 affected members and were normal in 2 of 2 healthy relatives. Magnetic resonance imaging abnormalities were predominantly located in the subcortical frontal white matter. All patients had acute and recurrent nerve palsies, while clinical features of central nervous system involvement were not a characteristic of this pedigree. Conclusions: We demonstrate that this association, previously reported in sporadic cases, is not coincidental. Therefore, patients with hereditary neuropathy with liability to pressure palsies can present central nervous system white matter lesions, and the role of the PMP22 (peripheral myelin protein 22) gene deletion in the central nervous system should be further studied.
文摘周围髓鞘蛋白22基因(peripheral myelin protein-22,PMP22)相关性周围神经病是一组以PMP22基因突变导致的遗传性周围神经病,不同的突变类型是导致不同的临床表型的关键,大致可以分为五类:PMP22片段重复突变导致腓骨肌萎缩症1A型(Charcot-Marie-Tooth type-1A,CMT1A),PMP22缺失突变所致遗传性压迫易感性神经病(hereditary neuropathy with liability to pressure palsies,HNPP),PMP22基因点突变可引起CMT1E以及Dejerine-Sottas综合征(DSS)、Roussy-Levy综合征(RLS)等。本文就PMP22基因相关性周围神经病的临床及遗传学特点做一综述。
