Autosomal dominant sensory/motor neuropathy with ataxia (SMNA): Linkage to chromosome 7q22-q32
Autosomal dominant sensory/motor neuropathy with ataxia (SMNA): Linkage to chromosome 7q22-q32
复制标题
DOI：
10.1002/ajmg.10361
复制
发表时间：
2002-05-08
期刊：
影响因子：
--
通讯作者：
Raskind, WH
中科院分区：
文献类型：
--
作者：
Brkanac, Z;Fernandez, M;Raskind, WH
常染色体显性遗传性脊髓小脑共济失调和遗传性感觉神经病是两种异质性疾病，其临床、电生理和神经病理特征各异。SCA的临床特征是缓慢进行性步态不协调，通常伴有手、言语和眼睛的协调性差。周围神经病变不是SCA综合征的常见部分。相比之下，HSN的主要特征是进行性感觉丧失。在各种SCA和各种HSN之间存在大量的临床重叠，并且它们通常不能基于临床或神经成像研究进行区分。我们已经确定了一个五代美国家庭的爱尔兰血统与一个独特的神经系统疾病显示AD的遗传模式。症状的表现力和严重程度各不相同，包括感觉丧失、共济失调、锥体束征和肌无力。神经传导研究与感觉轴索神经病变一致。肌肉活检显示神经源性萎缩，脑MRI显示轻度小脑萎缩。为了确定责任基因座，我们进行了全基因组连锁分析。在分析了114个标记后，检测到与D 7S 486的连锁，在θ = 0.00处的两点LOD得分为4.79。对该区域中其他标志物的评价提供了标志物D 7S 2554在θ = 0.00时的最大LOD评分6.36。单倍型分析在7 q22-q32之间的标记D 7S 2418和D 7S 1804与该疾病共分离，该区域约为14 cM。由于这种疾病不容易落入SCA或HSN类别，因此将其命名为共济失调感觉/运动神经病（SMNA）。(C)2002 Wiley-Liss，Inc.
The autosomal dominant (AD) spinocerebellar ataxias (SCAs) and hereditary sensory neuropathies (HSN) are heterogeneous disorders characterized by variable clinical, electrophysiological, and neuropathological profiles. The SCAs are clinically characterized by slowly progressive incoordination of gait often associated with poor coordination of hands, speech, and eyes. Peripheral neuropathy is not a frequent part of the SCA syndrome. In contrast, the HSNs are primarily characterized by progressive sensory loss. There is substantial clinical overlap between the various SCAs and the various HSNs, and they often cannot be differentiated on the basis of clinical or neuro-imaging studies. We have identified a five-generation American family of Irish ancestry with a unique neurological disorder displaying an AD pattern of inheritance. There was variable expressivity and severity of symptoms including sensory loss, ataxia, pyramidal tract signs, and muscle weakness. Nerve conduction studies were consistent with a sensory axonal neuropathy. Muscle biopsy revealed neurogenic atrophy and brain MRI showed mild cerebellar atrophy. To identify the responsible locus we pursued a whole genome linkage analysis. After analyzing 114 markers, linkage to D7S486 was detected with a two point LOD score of 4.79 at theta = 0.00. Evaluation of additional markers in the region provided a maximum LOD score of 6.36 at theta = 0.00 for marker D7S2554. Haplotype analysis delimited an approximately 14-cM region at 7q22-q32 between markers D7S2418 and D7S1804 cosegregating with the disease. Because this disorder does not easily fall into either the SCA or HSN categories, it is designated sensory/motor neuropathy with ataxia (SMNA). (C) 2002 Wiley-Liss, Inc.