遗传性痉挛性截瘫伴胼胝体发育不良的遗传学研究进展

遗传性痉挛性截瘫伴胼胝体发育不良（HSP-TCC）是复杂型HSP的一种,临床特点为进行性双下肢痉挛伴胼胝体发育不良,多儿童及青少年发病,常伴智能障碍。HSP-TCC具有高度的遗传异质性,病理提示皮质脊髓束变性。目前已发现至少19个疾病基因,主要包括：SPG1、SPG11、SPG15、SPG21、SPG35、SPG44、PG47、SPG54、SPG56等。该文就近年来有关该病的遗传学研究进展进行了综述,以期有助于该病的鉴别与诊断。     

遗传性痉挛性截瘫伴薄胼胝体6例报道并文献复习

目的探讨遗传性痉挛性截瘫伴薄胼胝体(HSP-TCC)的发病机制、临床特点、影像学表现及预后。方法分析6例HSP-TCC患者的临床及影像学表现,结合文献复习总结其临床特征。结果 6例患者均青少年起病,表现为痉挛步态,腱反射亢进,病理征阳性,2例有共济失调。患者均无感觉障碍及大小便障碍。全部患者头颅MRI显示胼胝体变薄。结论 HSP-TCC作为复杂型遗传性痉挛性截瘫(HSP)的一种,临床上以双下肢痉挛性截瘫和薄胼胝体为特征,发病机制尚不清楚,预后较差。     

遗传性痉挛性截瘫伴薄型胼胝体的临床特征

目的 探讨遗传性痉挛性截瘫伴薄型胼胝体（HSP-TCC）的临床特征。方法 对4例HSP-TCC患者的临床资料进行回顾性分析。结果 4例患者均于青少年起病，表现为智能低下，痉挛步态，双下肢痉挛，无力，腱反射亢进，病理征阳性，无感觉障碍，2例有共济失调及大小便障碍；1例有双上肢痉挛及肌肉萎缩，头颅MRI显示胼胝体变薄。结论 HSP-TCC的主要临床特征为青少年起病的痉挛性截瘫，智能低下，头颅MRI显示胼胝体变薄。     

遗传性痉挛性截瘫伴胼胝体发育不良六例的临床特征与maspardin基因突变分析

遗传性痉挛性截瘫伴胼胝体发育不良（hereditary spastic paraplegia with thin corpus callosum，HSP-TCC）是一种常染色体隐性（AR）遗传的复杂型HSP，临床极为罕见，青少年发病，表现为缓慢进展的痉挛性截瘫伴痴呆，晚期可出现肌萎缩、小脑及锥体外系症状等，头部磁共振成像（MRI）示胼胝体发育不良和脑萎缩，多见于日本。Mast综合征也是一种AR遗传的复杂型HSP，儿童或青少年发病，     

遗传性痉挛性截瘫合并胼胝体发育不良及灰质异位一例

<正>临床资料患者男性,39岁,因双下肢无力、走路不稳10年入院,自10年前无明显诱因出现双下肢无力,走路不稳,症状逐渐加重,多次摔倒,以向左侧为多,走直线困难,伴有头晕,无恶心呕吐,无踩棉花感。近1年来症状加重,体重减轻26斤,便秘,2周1次,小便频、急,曾尿失禁。顺产,无产伤。儿时体质较弱,但体     

散发性遗传性痉挛性截瘫8型一例并文献复习

遗传性痉挛性截瘫（hereditary spastic paraplegia , HSP）,又称Strümpell‐Lorrain病,是一种比较少见的家族遗传性变性病。本院2013‐08收治1例散发性 H S P ,根据基因检测结果,致病基因定位在 SPG8的位点,即 KI‐AA0196基因,且在KIAA0196基因发现c.711＋3＞ A杂合剪切变异。本文结合国内外相关文献复习总结 HSP的临床特征、分型及致病基因特点。     

遗传性痉挛性截瘫

遗传性痉挛性截瘫 (HSPS) ,也称作Strumpell -Lorrain病 ,是一组罕见的以显著的临床及遗传异质性为特征的疾病。自 1883年被初次描述以来已发现了多种的临床形式。单纯型表现为反射活跃 ,Babinski征 ,双下肢的痉挛及运动缺损通常伴有弓行足 ,深感觉损害 ,括约肌障碍 ,有时有上肢辩距障碍。其他形式称为复杂型 ,指表现为一种或几种神经或神经外特征。现已弄清其他神经变性疾病也可存在与复杂型HSP相似的表现型 ,如成人Friedreich’s共济失调和肌萎缩性侧索硬化症 (ALS) ,故这些疾病的分类不仅要靠临床而且要依赖遗传模式 (常染色体显性…     

遗传性痉挛性截瘫1个家系报告

遗传性痉挛性截瘫１个家系报告董海波韩漫夫布茂利遗传性痉挛性截瘫临床上较少见。我们遇见一个家系２代３人发病，仅以双下肢痉挛性瘫痪为首发症状，现报告如下。先证者Ⅲ１，男性，３５岁。１９９７年６月２７日入院。患者于１０年前开始出现跑步停止受限，身体向前倾斜...     

SPAST基因新位点突变致遗传性痉挛性截瘫的家系报道

目的 分析SPAST基因突变引起的遗传性痉挛性截瘫(HSP),提高临床医生对该病的认识。方法 回顾性分析1个2020年7月就诊于山东大学齐鲁医院最终确诊为HSP 4型的家系,明确致病基因,分析其临床表现,并复习相关文献。结果 患者及其母亲在SPAST基因第8外显子区域携带一处单杂合变异：c.1105A>C(腺嘌呤>胞嘧啶),导致氨基酸改变p.T369P(苏氨酸>脯氨酸)。SPAST基因c.1105A>C杂合突变可能为其家系致病性变异。结论 该家系携带的SPAST基因c.1105A>C杂合突变可能为其家系发病的原因。     

中国遗传性痉挛性截瘫的临床特点

目的 明确我国腓骨肌萎缩症的临床特点。方法 总结国内文献中报道的７８个家族，３５４例２及我院３９个家族、８１列患者的临床资料。结果 男：女约为１．７７：１，家族史阳性率６２．４％，其中常显、常隐、Ｘ隐性遗传分别为４１、１３、２个家系，同一家族患者发病年龄具有很高相关性。发病年龄１个月￣５５岁，平均１０．６岁，其中１￣２０岁起病占７１．２％；剪刀样步态７９．１％、双下肢肌张力增高８２．３％、肌力下降     

Thinning of the Corpus Callosum and Cerebellar Atrophy is Correlated with Phenotypic Severity in a Family with Spastic Paraplegia Type 11

Background

Mutations in the spatacsin gene are associated with spastic paraplegia type 11 (SPG11), which is the most-common cause of autosomal recessive hereditary spastic paraplegia. Although SPG11 has diverse phenotypes, thinning of the corpus callosum is an important feature.

Case Report

Clinical, genetic, and radiological evaluations were undertaken in a large family from Gujarat in North India with hereditary spastic paraplegia, whose affected members presented with varying degrees of spasticity, ataxia, and cognitive impairment. The clinical severity and the degree of corpus callosum and cerebellar atrophy varied among the four affected individuals in the family. Genetic testing of the affected members revealed recessive mutations in the spatacsin gene, consistent with a diagnosis of SPG11.

Conclusions

We believe that the extent of corpus callosum thinning and cerebellar atrophy is correlated with disease severity in affected patients. The addition of extrapyramidal features in the most-affected members suggests that SPG11 exhibits considerable phenotypic heterogeneity.     

Hereditary Spastic Paraplegia in Koreans: Clinical Characteristics and Factors Influencing the Disease Severity

Background and PurposeHereditary spastic paraplegia (HSP) progresses over time and is associated with locomotive dysfunction. Understanding the factors affecting disease severity and locomotive function is important in HSP. This study investigated the factors influencing disease severity and ambulation status of HSP.MethodsWe consecutively enrolled 109 Korean patients (64 males, and 45 females)from 84 families with a clinical diagnosis of HSP. HSP was primarily diagnosed based on clinical criteria including clinical findings, family history, and supported by genetic studies. Epidemiological and clinical features of the patients were analyzed, and the Spastic Paraplegia Rating Scale (SPRS) score and ambulatory status were used to evaluate disease severity.ResultsNinety-two (84.4%) patients had pure HSP, and 55 (50.4%) had a dominant family history. Thirty-one (28.4%) patients required a mobility aid for locomotion. A Kaplan-Meier analysis showed that HSP patients lost their independent gait ability after a median disease duration of 34 years. Those with an age at onset of ≤18 years had a longer median independent walking time. Pure HSP is characterized by predominant bilateral lower extremity weakness and spasticity, whereas complicated HSP presents more complex neurological findings such as ocular and bulbar symptoms, ataxia, and cognitive impairment. Complicated HSP was significantly correlated with the SPRS mobility score (β=3.70, 95% confidence interval=0.45–6.94). The age at onset and disease duration were significantly correlated with disease severity, and they were significant predictors of the use of a mobility aid (p<0.05).ConclusionsThese findings suggest that a later age at onset and longer disease duration are significant factors affecting the disease severity and ambulatory function in patients with HSP. These findings can help clinicians to identify subjects at risk of locomotive impairment.     

Spastic paraplegia with thin corpus callosum: description of 20 new families, refinement of the SPG11 locus, candidate gene analysis and evidence of genetic heterogeneity

We studied 20 Mediterranean families (40 patients) with autosomal recessive hereditary spastic paraplegia and thin corpus callosum (ARHSP-TCC, MIM 604360) to characterize their clinical and genetic features. In six families (17 patients) of Algerian Italian, Moroccan, and Portuguese ancestry, we found data consistent with linkage to the SPG11 locus on chromosome 15q13–15, whereas, in four families (nine patients of Italian, French, and Portuguese ancestry) linkage to the SPG11 locus could firmly be excluded, reinforcing the notion that ARHSP-TCC is genetically heterogeneous. Patients from linked and unlinked families could not be distinguished on the basis of clinical features alone. In SPG11-linked kindred, haplotype reconstruction allowed significant refinement to 6 cM, of the minimal chromosomal interval, but analysis of two genes (MAP1A and SEMA6D) in this region did not identify causative mutations. Our findings suggest that ARHSP-TCC is the most frequent form of ARHSP in Mediterranean countries and that it is particularly frequent in Italy.Electronic Supplementary Material  Supplementary material is available for this article at     

SPG11: a consistent clinical phenotype in a family with homozygous Spatacsin truncating mutation

Hereditary spastic paraplegias (HSP) are a heterogeneous group of neurodegenerative disorders leading to progressive spasticity of the lower limbs. Here, we describe clinical and genetic features in an Italian family affected by autosomal recessive HSP (ARHSP) with mental impairment and thin corpus callosum (TCC). In both affected subjects, genetic analysis revealed the presence of a homozygous small deletion (733_734delAT) leading to a frameshift (M245VfsX) within the coding region of SPG11 gene, encoding spatacsin. This finding is the first independent confirmation that spatacsin loss of function mutations cause ARHPS-TCC. Roberto Del Bo and Alessio Di Fonzo, These two authors equally contributed to the present work.     

遗传性痉挛性截瘫2家系的临床特点与spastin基因突变分析

目的:探讨2个家系遗传3代以上常染色体显性遗传性痉挛性截瘫(AD-HSP)的临床特点及其与spastin基因突变的关系。方法:对2个AD-HSP家系进行详细的临床检查,总结所有患者临床特点,并应用PCR技术结合DNA序列分析方法,检测2家系先证者spastin基因的突变情况。结果:2家系中所有患者均具有HSP的典型表现,PCR-DNA序列分析2例先证者spastin基因的17个外显子均未发现有异常突变。结论:2家系HSP患者具有典型的AD-HSP临床表现,并非spastin基因外显子突变所致。     

SPG11 spastic paraplegia

Autosomal recessive hereditary spastic paraplegia (AR HSP) with thin corpus callosum (TCC) is a rare neurodegenerative disorder often caused by mutations in the gene encoding for spatacsin at the SPG11 locus on chromosome 15q. The disease is characterized by progressive spastic paraparesis and mental retardation which occur during the first two decades of life and frequently with peripheral neuropathy. Brain magnetic resonance imaging (MRI) reveals typical TCC with periventricular white matter changes. We describe two patients, of Turkish descent, from the same consanguineous family and affected with SPG11 in association with unusual early-onset parkinsonism. Parkinsonism occurred during the very early stages of SPG11 in both patients, being in one the inaugural symptom of the disease presented as a resting tremor with akinesia, rigidity and expressing an initial moderate levodopa-response that progressively weakened. The second patient presented a resting tremor with mild akinesia and no levodopa-response. Both patients were affected with progressive spastic paraparesis which had initially occurred at 15 and 12 years of age, respectively, in association with mild mental retardation and an axonal polyneuropathy. TCC with periventricular white matter changes (PWMC) was evident by MRI and ¹²³I-ioflupane SPECT was abnormal. Genetic analysis detected for both patients a new c.704_705delAT, p.H235RfsX12 homozygous mutation in SPG11. This report provides evidence that parkinsonism may initiate SPG11-linked HSP TCC and that SPG11 may cause juvenile parkinsonism.