A new locus for a childhood onset, slowly progressive autosomal recessive spinocerebellar ataxia maps to chromosome 11p15
A new locus for a childhood onset, slowly progressive autosomal recessive spinocerebellar ataxia maps to chromosome 11p15
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DOI：
10.1136/jmg.2004.019232
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发表时间：
2004-11-01
影响因子：
4
通讯作者：
Maat-Kievit, JA
中科院分区：
文献类型：
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作者：
Breedveld, GJ;van Wetten, B;Maat-Kievit, JA
小脑性共济失调是一组异质性的神经退行性疾病，以小脑变性的症状和体征、锥体和锥体外系特征以及可变的多发性神经病为特征。突出的临床特征是小脑性共济失调的迹象，如步态不协调和手部、言语和眼睛运动的不受控制的协调，而(额外的)锥体体征，如视网膜、心脏、肌肉和/或神经元受累，则不太常见。临床照片显示了发病年龄和疾病进展的很大差异。散发性共济失调可归因于各种中毒、炎症、副肿瘤、代谢、内分泌或吸收不良。遗传性共济失调由大量常染色体显性共济失调和常染色体隐性X连锁遗传方式组成。其余原因不明的共济失调称为特发性散发性小脑性共济失调。大多数有症状的共济失调可以根据典型的病史或通过简单的实验室测试来诊断。在遗传性共济失调中，家族史很重要。然而，阴性的家族史不能排除常染色体隐性遗传或X连锁共济失调，甚至常染色体显性遗传性共济失调可能会因为外显性降低、基因携带者在症状出现之前过早死亡、印记效应、可变表达、收养或非父子关系而被漏掉。1已鉴定出几种遗传型的基因缺陷。常染色体显性遗传性共济失调常与含有不稳定扩增三核苷酸重复序列的基因有关，如SCA1、2、3、6、7、17和DRPLA1、2、3、6、7、17和SCA8、10、12(非)编码区的编码CAG重复序列的多个谷氨酰胺重复序列的扩增，或SCA 8、10、12(非)编码区的三核苷酸或五核苷酸重复序列的扩增。2 3一些常染色体隐性遗传性共济失调的临床特征，其基因定位，或其基因及其蛋白的鉴定(表1)。2-4常染色体隐性共济失调最常见的形式(11-38%)是Friedreich‘s共济失调(FRDA)，5-8表现出较大的临床表现差异，即发病年龄和临床症状的严重程度。其他形式的常染色体隐性共济失调是共济失调远血管扩张症(AT)9或AT样疾病，共济失调伴单独维生素E缺乏(AVED)10例，失脂蛋白血症(ABL)11例，痉挛性Charlevoix-Saguenay共济失调(ARSACS)12例，婴儿起病脊髓小脑性共济失调(IOSCA)13 14例，共济失调伴动眼失用症15例(AOA1和2)，16 17和Refsum病(Rd)。18 19此外，遗传性代谢障碍可引起共济失调样碳水化合物缺乏性糖结合综合征、20 21 GM2神经节苷脂沉着症、22和其他疾病(表1)。2-4
The cerebellar ataxias are a heterogeneous group of neurodegenerative disorders, characterised by symptoms and signs of cerebellar degeneration, pyramidal and extrapyramidal features, and variable polyneuropathy. Prominent clinical features are signs of cerebellar ataxia, such as uncoordinated gait and uncontrolled co-ordination of hand, speech, and eye movements, while (extra) pyramidal signs, such as retinal, cardiac, muscle and/or neuronal involvement, are less common. The clinical picture shows a large variation in age at onset and disease progression. Sporadic ataxias may be attributed to various toxic, inflammatory, paraneoplastic, metabolic, endocrinal, or malabsorption conditions. Hereditary ataxias consist of a large number of autosomal dominant ataxias and ataxias with an autosomal recessive and X-linked mode of inheritance. The remaining ataxias of unknown cause are referred to as idiopathic sporadic cerebellar ataxias. Most symptomatic ataxias can be diagnosed on the basis of a typical history or by simple laboratory tests. In hereditary ataxias family history is important. However, a negative family history cannot rule out autosomal recessive or X-linked ataxia and even autosomal dominantly inherited ataxia may be missed because of reduced penetrance, the early death of gene carriers before the onset of symptoms, imprinting effects, variable expression, adoption, or nonpaternity. 1Gene defects have been identified for several hereditary forms. Autosomal dominant ataxias are often associated with genes containing unstable expanded trinucleotide repeats, such as polyglutamine-coding CAG repeat expansions in SCA 1, 2, 3, 6, 7, 17 and DRPLA, or trinucleotide or pentanucleotide repeat expansions in (non-) coding regions in SCA 8, 10, and 12. Other mutations have been identified, such as point mutations in FGF14 and SCA14, and several loci, such as SCA 4, 5, 11, 13, 15, 16, 18, 19, 21, 22, 23, and 25 have been mapped. 2 3 Some autosomal recessive ataxias have been clinically characterised, their genes localised, or their genes and their proteins identified (table 1). 2–4 The most common form (11–38%) of autosomal recessive ataxia is Friedreich’s ataxia (FRDA), 5–8 which shows a large variation in clinical presentation, that is age at onset and severity of clinical symptoms. Other forms of autosomal recessive ataxia are ataxia teleangiectasia (AT) 9 or AT-like disorders, 10 ataxia with isolated vitamin E deficiency (AVED), 11 abetalipoproteinaemia (ABL), 12 spastic ataxia of Charlevoix-Saguenay (ARSACS), 13 14 infantile onset spinocerebellar ataxia (IOSCA), 15 ataxia with oculomotor apraxia (AOA1 and 2), 16 17 and Refsum’s disease (RD). 18 19 Furthermore, inherited metabolic disorders can cause ataxia-like carbohydrate deficient glycoconjugate syndrome, 20 21 GM2 gangliosidosis, 22 and other disorders (table 1). 2–4