Journal of the Peripheral Nervous System最新文献_第3页

Nonsystemic Vasculitic Neuropathy—A Brazilian Case Series 非全身性血管性神经病-巴西病例系列。

IF 3.2 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Peripheral Nervous System

Pub Date : 2025-12-09 DOI: 10.1111/jns.70086

Victor Evangelista Rodrigues Pereira, Roberto Pereira Santos, Marcos Raimundo Gomes de Freitas, Manuella Lima Gomes Ochtrop, Ana Caroline Siquara-De-Souza, Salim L. Balassiano, Marcia Rodrigues Jardim

Background and Aims

Vasculitides are a heterogeneous group of immune-mediated inflammatory disorders that compromise the vascuar wall, leading to luminal narrowing and tissue ischemia. When inflammation selectively affects the vasa nervorum without systemic involvement, it results in nonsystemic vasculitic neuropathy (NSVN), an underrecognized condition. NSVN presents diagnostic challenges due to its variable clinical manifestations and reliance on nerve biopsy for definitive diagnosis. This study aimed to characterize the clinical, neurophysiological, and histopathological features of NSVN in a Brazilian cohort.

Methods

We conducted a cross-sectional, ambispective cohort study combining retrospective chart review and prospective patient assessments. Inclusion required histopathological confirmation of isolated peripheral nerve vasculitis; cases with systemic or secondary vasculitis were excluded. Data collection included clinical evaluation, neurophysiology, and nerve biopsy.

Results

A total of 14 patients were included (9 female, 64%; mean age: 61). Most (n = 8, 57%) had subacute onset of painful sensory or sensorimotor deficits. Multiple mononeuropathies predominated (n = 11, 78%), but a subset exhibited chronic progression (n = 5, 35%) and axonal polyneuropathy (n = 3, 21%). Electrophysiological studies revealed a consistent axonal pattern. Biopsies confirmed possible vasculitis in six (43%), and probable vasculitis in six (42%), with only two (14%) fulfilling criteria for definite vasculitis. Serologies were nonspecific. Treatment involved corticosteroid pulse therapy, with immunosuppression in refractory cases.

Interpretation

These findings highlight that NSVN often presents with painful sensorimotor symptoms and may clinically mimic progressive axonal polyneuropathies. Given its potential for significant morbidity if left untreated, early recognition and consideration of nerve biopsy remain critical. The diagnostic complexity and variability in presentation suggest that NSVN may be underrecognized. We hope this cohort contributes to a broader understanding of its clinical spectrum and informs future diagnostic strategies.

背景和目的：血管炎是一种异质免疫介导的炎症性疾病，损害血管壁，导致管腔狭窄和组织缺血。当炎症选择性地影响血管神经而不累及全身时，它会导致非全身性血管性神经病（NSVN），这是一种未被认识的疾病。NSVN由于其多变的临床表现和对神经活检的明确诊断的依赖，提出了诊断挑战。本研究旨在描述巴西队列中NSVN的临床、神经生理和组织病理学特征。方法：我们进行了一项横断面、双视角队列研究，结合回顾性图表回顾和前瞻性患者评估。孤立性周围神经血管炎需要组织病理学证实；排除全身性或继发性血管炎病例。数据收集包括临床评估、神经生理学和神经活检。结果：共纳入14例患者，其中女性9例，占64%，平均年龄61岁。大多数（n = 8.57%）有亚急性发作的疼痛感觉或感觉运动缺陷。多发性单神经病变占主导地位（n = 11,78%），但一小部分表现为慢性进展（n = 5,35%）和轴突多神经病变（n = 3,21%）。电生理研究显示了一致的轴突模式。活检证实6例（43%）可能有血管炎，6例（42%）可能有血管炎，只有2例（14%）符合明确的血管炎标准。血清学无特异性。治疗包括皮质类固醇脉冲治疗，对难治性病例进行免疫抑制。解释：这些发现强调NSVN通常表现为疼痛的感觉运动症状，并且在临床上可能类似于进行性轴突多发性神经病。如果不及时治疗，其潜在的显著发病率，早期识别和考虑神经活检仍然是至关重要的。诊断的复杂性和表现的可变性表明NSVN可能未被充分认识。我们希望这个队列有助于更广泛地了解其临床谱，并告知未来的诊断策略。

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引用次数: 0

Novel Dominant Splicing Variant in MPZ Associated With Unusual Charcot–Marie–Tooth Disease 与不寻常的腓骨-玛丽-牙病相关的MPZ显性剪接新变异。

IF 3.2 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Peripheral Nervous System

Pub Date : 2025-12-09 DOI: 10.1111/jns.70085

Anthony Maino, Florence Hazane-Puch, Philippe Petiot, Nathalie Roux-Buisson, John Rendu, Julien Fauré, Gaëlle Hardy

Background and Aims

Variants in the myelin protein zero coding MPZ gene are responsible for a broad spectrum of peripheral demyelinating and axonal neuropathies, including different types of Charcot–Marie–Tooth diseases, challenging for genotype–phenotype correlation.

Methods

Minigene splicing reporter assay was used to unveil the pathogenic mechanism of a novel MPZ(NM_000530.8) c.234 + 1G>C p.(?) heterozygous splice variant.

Results

The variant was identified in a 47-year-old female patient presenting with atypical clinical features, including balance disturbance with positive Romberg, absent Achilles tendon reflexes, distal hypoesthesia and bulbar involvement, including dysarthria and dysphagia. Electromyography revealed a sensory-motor neuropathy with moderately reduced nerve conduction velocities. In silico analysis predicted this variant to disrupt the consensual donor splice site located in intron 2 of MPZ. Minigene construction confirmed the functional impact of this variant, revealing exon 2 skipping and the apparition of a premature termination codon.

Interpretation

This case expends the genotype–phenotype correlations of MPZ-related Charcot–Marie–Tooth diseases, associating atypical mild phenotype with a rare splice dominant variant, and provides new insights into MPZ haploinsufficiency and pathogenic mechanisms.

背景和目的：髓鞘蛋白零编码MPZ基因的变异是广泛的外周脱髓鞘和轴突神经病变的原因，包括不同类型的沙科-玛丽-牙病，对基因型-表型相关性具有挑战性。方法：采用Minigene剪接报告基因试验，揭示新型MPZ(NM_000530.8) C .234 + 1G>C . p.（?）杂合剪接变异的致病机制。结果：该变异在一名47岁女性患者中被发现，其临床特征不典型，包括平衡障碍，Romberg阳性，跟腱反射缺失，远端感觉减退和球受累，包括构音障碍和吞咽困难。肌电图显示感觉-运动神经病变，神经传导速度中度降低。计算机分析预测这种变异会破坏位于MPZ内含子2上的供体剪接位点。miniigene的构建证实了该变异的功能影响，揭示了外显子2的跳跃和一个过早终止密码子的出现。解释：本病例扩展了MPZ相关沙克-玛丽-图斯病的基因型-表型相关性，将非典型轻度表型与罕见的剪接显性变异联系起来，并为MPZ单倍性不足和致病机制提供了新的见解。

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引用次数: 0

Human Cytomegalovirus Associated Neuropathies: A Comprehensive Review From Pathophysiology to Clinical and Therapeutic Considerations 人类巨细胞病毒相关神经病变：从病理生理学到临床和治疗考虑的综合综述。

IF 3.2 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Peripheral Nervous System

Pub Date : 2025-12-08 DOI: 10.1111/jns.70087

Naomi Behanan, Sarab Mohamed, Rhona Chen, Gloria Mak, Jian-Qiang Lu

Human cytomegalovirus (HCMV) is a neurotropic, double-stranded DNA virus from the Herpesviridae family. It has a large genome, infects the majority of populations, and typically causes asymptomatic infections in healthy individuals. After the initial infection with established lifelong latency, HCMV can reactivate and cause disorders including neuropathies. Besides the infections typically in immunocompromised patients, HCMV may also trigger autoimmunity leading to tissue injury and associated pathologies. HCMV-associated neuropathies are a pathogenically heterogeneous group of peripheral nervous system (PNS) disorders that include direct HCMV infection of the nerve(s), as well as non-infectious associated neuropathies such as axonal or degenerative, vasculitic/ischemic or necrotizing, inflammatory demyelinating, and immune-mediated forms. Congenital HCMV-associated neuropathies primarily involve the cochlear/auditory and optic nerves with somewhat distinct pathogenic mechanisms compared with their postnatal counterparts, largely due to the immaturity of the fetal immune system. This article reviews the pathophysiology of PNS involvement in HCMV infection, followed by congenital HCMV-associated neuropathies with a case demonstration, and various postnatal HCMV-associated neuropathies, including a detailed review of HCMV-associated optic neuropathies, from pathogenic mechanisms to clinical and therapeutic implications. As the PNS has a few immune protective mechanisms against pathogens, direct HCMV infection of nerves is rare and occurs only in immunocompromised patients; most HCMV-associated neuropathies are secondary with multiple pathogenic mechanisms including varying degrees of autoimmunity. While the clinical manifestations of HCMV-associated neuropathies are variable, their treatment is typically empirical and case-based, focusing on antiviral therapy often combined with immunomodulatory approaches. Prompt and appropriate management can improve outcomes of HCMV-associated neuropathies.

人巨细胞病毒（HCMV）是疱疹病毒科的一种嗜神经双链DNA病毒。它有一个大的基因组，感染大多数人群，并且通常在健康个体中引起无症状感染。初次感染具有确定的终身潜伏期后，HCMV可重新激活并引起包括神经病变在内的疾病。除了免疫功能低下患者的典型感染外，HCMV还可能引发自身免疫，导致组织损伤和相关病理。HCMV相关神经病是一组病理异质性的外周神经系统（PNS）疾病，包括直接感染神经的HCMV，以及非感染性相关神经病，如轴突或退行性、血管/缺血性或坏死性、炎症性脱髓鞘和免疫介导形式。先天性hcmv相关的神经病变主要涉及耳蜗/听觉和视神经，与出生后的病变相比，其致病机制有所不同，主要是由于胎儿免疫系统不成熟。本文综述了PNS参与HCMV感染的病理生理学，随后是先天性HCMV相关神经病的病例论证，以及各种出生后HCMV相关神经病，包括HCMV相关视神经病变的详细综述，从致病机制到临床和治疗意义。由于PNS对病原体的免疫保护机制很少，因此HCMV直接感染神经是罕见的，仅发生在免疫功能低下的患者中；大多数hcmv相关的神经病变是继发性的，具有多种致病机制，包括不同程度的自身免疫。虽然hcmv相关神经病变的临床表现是可变的，但其治疗通常是经验和病例为基础的，重点是抗病毒治疗，通常结合免疫调节方法。及时和适当的治疗可以改善hcmv相关神经病变的预后。

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引用次数: 0

A Case of Retinopathy–Sensory Neuropathy Syndrome With a Novel Compound Heterozygous FLVCR1 Variant 视网膜病变-感觉神经病变综合征伴新型复合杂合FLVCR1变异体1例。

IF 3.2 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Peripheral Nervous System

Pub Date : 2025-12-02 DOI: 10.1111/jns.70082

Yumiko Nakano, Yusuke Fukui, Kentaro Deguchi, Chika Matsuoka, Tomohito Kawano, Yuki Taira, Ayaka Matsuo, Yosuke Osakada, Taijun Yunoki, Emi Nomura, Mami Takemoto, Ryuta Morihara, Toru Yamashita, Hiroyuki Ishiura

Background and Aims

Retinopathy–sensory neuropathy syndrome (RETSNS), also known as posterior column ataxia with retinitis pigmentosa (PCARP), is a rare neurodegenerative disorder that is caused by biallelic pathogenic variants in FLVCR1. Here, we report a case of a Japanese patient with RETSNS.

Methods

Clinical, neuroradiological, and electrophysiological findings were documented. Whole-genome sequencing was performed. Subcloning was carried out to confirm compound heterozygosity. A functional assay was performed to assess the pathogenicity of the variants.

Results

The patient showed retinitis pigmentosa and sensory ataxia. Over the course of the disease, autonomic dysfunction has become increasingly evident. Despite consanguinity in the family, whole-genome sequencing identified two heterozygous variants in FLVCR1 (c.369T>G, p.Phe123Leu and c.733A>G, p.Asn245Asp). Cloning of the PCR product followed by Sanger sequencing indicated compound heterozygosity of the variants. Immunocytochemistry of HEK293FT cells transfected with plasmids containing wild-type or variant FLVCR1 cDNA demonstrated altered subcellular localization of the variant FLVCR1 proteins, characterized by reduced membrane localization.

Interpretation

We report a novel variant in FLVCR1 causing RETSNS. The functional assay supports the pathogenicity of the variants.

背景和目的：视网膜病变-感觉神经病变综合征（RETSNS），也称为视网膜色素变性后柱共济失调（PCARP），是一种罕见的神经退行性疾病，由FLVCR1双等位基因致病变异引起。在此，我们报告一例日本的RETSNS患者。方法：记录临床、神经放射学和电生理表现。进行全基因组测序。亚克隆证实了复合杂合性。进行了功能分析以评估变异的致病性。结果：患者表现为色素性视网膜炎和感觉共济失调。在病程中，自主神经功能障碍越来越明显。尽管在家族中有血缘关系，但全基因组测序鉴定出FLVCR1的两个杂合变异（c.369T>G, p.Phe123Leu和c.733A>G, p.Asn245Asp）。克隆后进行Sanger测序，结果表明该变异具有复合杂合性。用含有野生型或变异FLVCR1 cDNA的质粒转染HEK293FT细胞的免疫细胞化学结果显示，变异FLVCR1蛋白的亚细胞定位发生了改变，其特征是膜定位减少。解释：我们报道了FLVCR1引起RETSNS的一个新变异。功能分析支持变异的致病性。

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引用次数: 0

ITPR1 Deletion in a Patient With Sensory Ataxic Neuropathy and Sjögren Syndrome ITPR1缺失在感觉共济失调神经病和Sjögren综合征患者中的作用

IF 3.2 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Peripheral Nervous System

Pub Date : 2025-12-01 DOI: 10.1111/jns.70083

Saif Haddad, Roy Poh, Jason Hehir, James M. Polke, Julian Blake, Mary M. Reilly

Background

Sensory ataxic neuropathies (SAN) are rare large fibre sensory neuropathies characterised by progressive sensory loss and ataxia. They may be inherited or acquired. When inherited they are more commonly seen as part of a broader syndrome involving cerebellar ataxia or mitochondrial dysfunction. Isolated inherited SAN are rare, and the causes are limited, including RFC1 expansions (CANVAS), POLG variants and variants in COX20 and RNF170. Spinocerebellar ataxia type 15 (SCA15), caused by deletions in the ITPR1 gene, is another potential genetic cause of SAN, as peripheral neuropathy is commonly associated with various spinocerebellar ataxias.

Methods

A 35-year-old female who presented with an asymmetrical upper limb predominant sensory ataxic neuropathy which had initially been treated as a vasculitic neuropathy at her local hospital, underwent further evaluation.

Results

Genetic analysis identified an approximately 6.5 Mb terminal deletion of chromosome 3p, including the ITPR1 gene.

Conclusions

This case report adds to the growing body of literature on ITPR1-related diseases, highlighting the phenotypic variability of ITPR1 and identifying it as a potential cause of isolated SAN. While a connection to Sjögren's syndrome cannot be excluded, the role of ITPR1 as the primary cause remains the focus. We propose that the neuropathy community consider screening SAN patients for ITPR1 deletions, as additional cases may help clarify its clinical significance.

背景：感觉共济失调神经病（SAN）是一种罕见的以进行性感觉丧失和共济失调为特征的大纤维感觉神经病。它们可能是遗传的，也可能是获得的。当遗传时，它们更常被视为涉及小脑共济失调或线粒体功能障碍的更广泛综合征的一部分。孤立的遗传性SAN很少见，原因也很有限，包括RFC1扩展（CANVAS）、POLG变异以及COX20和RNF170的变异。脊髓小脑共济失调15型（SCA15）由ITPR1基因缺失引起，是SAN的另一个潜在遗传原因，因为周围神经病变通常与各种脊髓小脑共济失调有关。方法：一名35岁的女性，她表现为不对称上肢主要感觉共济性神经病变，最初在当地医院作为血管性神经病变治疗，接受了进一步的评估。结果：遗传分析发现染色体3p末端缺失约6.5 Mb，包括ITPR1基因。结论：本病例报告增加了越来越多的关于ITPR1相关疾病的文献，强调了ITPR1的表型变异性，并确定其是孤立性SAN的潜在原因。虽然不能排除与Sjögren综合征的联系，但ITPR1作为主要原因的作用仍然是焦点。我们建议神经病变界考虑筛查SAN患者的ITPR1缺失，因为额外的病例可能有助于阐明其临床意义。

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引用次数: 0

Rethinking Neuropathy in TTC19 Mutations: The Need for Broader Differential Diagnosis 重新思考TTC19突变中的神经病变：需要更广泛的鉴别诊断。

IF 3.2 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Peripheral Nervous System

Pub Date : 2025-11-25 DOI: 10.1111/jns.70074

Christian Messina

引用次数: 0

Correction to “The Correlation Between Functional and Morphometric Small Fiber Assessment in Mixed Etiology Polyneuropathy” 更正“混合病因多发性神经病变的小纤维功能与形态学评估的相关性”。

IF 3.2 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Peripheral Nervous System

Pub Date : 2025-11-25 DOI: 10.1111/jns.70080

F. A. Ghadban, C. N. Bay-Smidt, A. Bjørnkær, et al., “The Correlation Between Functional and Morphometric Small Fiber Assessment in Mixed Etiology Polyneuropathy,” Journal of the Peripheral Nervous System 30, no. 3 (2025): e70051, https://doi.org/10.1111/jns.70051.

It has come to our attention that there was an error in the results section. Two patients had a warm detection threshold (WDT) of approximately 15, which is not possible as the range of this variable is 32–50. After reviewing our data, we also found that 17 patients had a WDT of 50.5 or 51, while the upper limit is 50. We have corrected the errors and re-analyzed the affected correlations as shown in Figures 1-3 and Tables 1–5 and Table S1.

We apologize for this error.

陈晓明，陈晓明，陈晓明，等，“小纤维在多神经病变中的功能和形态的相关性研究”，中华神经科学杂志，第30期。3 (2025): e70051, https://doi.org/10.1111/jns.70051.It引起了我们的注意，结果部分有一个错误。两名患者的温检测阈值（WDT）约为15，这是不可能的，因为该变量的范围为32-50。在回顾我们的资料后，我们还发现17例患者的WDT为50.5或51，而上限为50。我们已经修正了错误，并重新分析了图1-3、表1-5和表S1所示的受影响的相关性。我们为这个错误道歉。

引用次数: 0

Intravenous Efgartigimod or Intravenous Immunoglobulin in Guillain-Barre Syndrome: An Observational Multicenter Study 静脉注射依加替莫德或静脉注射免疫球蛋白治疗格林-巴利综合征：一项多中心观察性研究。

IF 3.2 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Peripheral Nervous System

Pub Date : 2025-11-24 DOI: 10.1111/jns.70072

Heting Cai, Fan Zhou, Tao Li, Zhijun Li, Jianfeng Luo, Jianian Hu, Min Deng, Chong Sun, Chongbo Zhao, Jie Lin

Background and Aims

Guillain-Barré syndrome (GBS) is an acute autoimmune polyradiculoneuropathy characterized by progressive flaccid paralysis. The standard treatments include intravenous immunoglobulin (IVIg) and plasma exchange (PE), with limited accessibility to these treatments. Efgartigimod is an FcRn antagonist that reduces IgG levels, similar to PE, serving as a potential alternative. This study aims to compare the efficacy of Efgartigimod with standard IVIg in GBS.

Methods

This was a multicenter observational study in China. Eligible participants were aged ≥ 16 years, meeting the diagnostic criteria for GBS, and presented with a GBS Disability Scale score ≤ 5 at baseline assessment. Participants received efgartigimod (10 mg/kg per week up to 4 doses) or IVIg (2 g/kg once). Outcomes were assessed at baseline, week 1, and week 2 post-treatment, and at the last follow-up. The primary efficacy endpoint was the proportion of participants improving at least 1 point on the GBS-DS.

Results

Between January and October 2024, 22 GBS patients were enrolled, including 11 in each group. At week 1, 14 patients improved in GBS-DS, with 7 (63.6%) in the efgartigimod group and 7 (63.6%) in the IVIg group. Median time to improvement was 4 days in the efgartigimod group and 8 days in the IVIg group. At week 2, GBS-DS response rates were 90.9% (10/11) for efgartigimod and 81.8% (9/11) for IVIg.

Interpretation

Based on our preliminary findings, intravenous efgartigimod may be potentially tolerated in GBS over the short term. However, this study cannot establish comparative efficacy given the methodological limitations, and large-scale well-controlled head-to-head trials remain imperative.

背景和目的：格林-巴勒综合征（GBS）是一种以进行性弛缓性麻痹为特征的急性自身免疫性多神经根神经病。标准治疗包括静脉注射免疫球蛋白（IVIg）和血浆置换（PE），但这些治疗的可及性有限。Efgartigimod是一种FcRn拮抗剂，可降低IgG水平，与PE类似，可作为潜在的替代药物。本研究旨在比较依加替莫德与标准IVIg治疗GBS的疗效。方法：这是一项中国的多中心观察性研究。符合条件的受试者年龄≥16岁，符合GBS诊断标准，基线评估时GBS残疾量表评分≤5分。参与者接受艾夫加替莫德（每周10mg /kg，最多4次）或IVIg （2g /kg，一次）。在基线、治疗后第1周、第2周和最后一次随访时评估结果。主要疗效终点是受试者在GBS-DS上改善至少1点的比例。结果：2024年1 - 10月，共纳入22例GBS患者，每组11例。在第1周，14例患者的GBS-DS得到改善，其中埃加替莫组7例（63.6%），IVIg组7例（63.6%）。艾加替莫德组的中位改善时间为4天，IVIg组的中位改善时间为8天。在第2周，艾加替莫德的GBS-DS缓解率为90.9% (10/11)，IVIg的缓解率为81.8%（9/11）。解释：根据我们的初步研究结果，静脉注射艾夫加替莫德可能在短期内对GBS有潜在的耐受性。然而，由于方法上的限制，本研究不能建立比较疗效，大规模的、控制良好的头对头试验仍然是必要的。

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引用次数: 0

Peter James Dyck: In Memoriam 彼得·詹姆斯·戴克：纪念

IF 3.2 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Peripheral Nervous System

Pub Date : 2025-11-19 DOI: 10.1111/jns.70073

P. James B. Dyck, William J. Litchy

引用次数: 0

Frequent De Novo Mutations in Korean Patients With Charcot–Marie–Tooth Disease 韩国腓骨肌萎缩症患者频繁的新生突变

IF 3.2 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Peripheral Nervous System

Pub Date : 2025-11-18 DOI: 10.1111/jns.70081

Ah Jin Lee, Soo Hyun Nam, Sinyeong Lee, Su Min Lee, Kyung Suk Lee, Byung-Ok Choi, Ki Wha Chung

Background and Aims

De novo mutations provide a fundamental source of gene pool changes, driving genomic microevolution. Charcot–Marie–Tooth disease (CMT), which is a group of genetically and clinically heterogeneous peripheral neuropathic disorders, is characterized by progressive muscle weakness, hand and foot deformities, and occasional involvement of other organs. This study conducted the first cohort study of de novo mutations in CMT patients.

Methods

De novo mutations were examined in 151 genetically diagnosed father–mother–child trio autosomal dominant CMT families except for CMT1A.

Results

We identified 49 de novo point or small indel mutations in 61 patients. The frequency of de novo mutations was 40.4%, with gene-specific rates in their distribution. Haplotype analysis revealed predominant paternal origin, consistent with previous reports for CMT1A. Frequent substitutions at highly methylated CpG sites suggested that CpG methylation strongly contributes to the induction of de novo mutations. In particular, this study observed an anticipation of earlier onset in the affected children compared to their parents (founders) with de novo mutations.

Interpretation

This study reports de novo mutations that occur frequently in CMT families. Characterization of de novo pathogenic mutations is expected to provide valuable insights not only into the genetic diagnosis and treatment of rare genetic diseases, but also into the evolutionary genomic study of deleterious alleles.

背景和目的：新生突变提供了基因库变化的基本来源，驱动基因组微进化。腓骨肌萎缩症（Charcot-Marie-Tooth disease， CMT）是一组遗传和临床异质性的周围神经病变，其特征是进行性肌肉无力、手脚畸形，偶尔累及其他器官。本研究首次对CMT患者的新生突变进行了队列研究。方法：对151例经遗传诊断的父亲-母亲-孩子三人常染色体显性CMT家族（除CMT1A外）进行从头突变检测。结果：我们在61例患者中发现了49个新生点或小indel突变。新生突变发生率为40.4%，具有基因特异性。单倍型分析显示CMT1A的主要父系起源，与先前的报道一致。在高度甲基化的CpG位点上频繁的替换表明，CpG甲基化强烈地促进了新生突变的诱导。特别是，本研究观察到，与父母（创始人）相比，受影响的儿童与新生突变相比，预期发病时间更早。解释：本研究报道了在CMT家族中经常发生的新生突变。新发致病性突变的特征不仅可以为罕见遗传疾病的遗传诊断和治疗提供有价值的见解，还可以为有害等位基因的进化基因组研究提供有价值的见解。

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引用次数: 0