A new locus (SPG47) maps to 1p13.2-1p12 in an Arabic family with complicated autosomal recessive hereditary spastic paraplegia and thin corpus callosum
A new locus (SPG47) maps to 1p13.2-1p12 in an Arabic family with complicated autosomal recessive hereditary spastic paraplegia and thin corpus callosum
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DOI：
10.1016/j.jns.2011.03.011
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发表时间：
2011-06-15
影响因子：
4.4
通讯作者：
Leshinsky-Silver, Esther
中科院分区：
文献类型：
--
作者：
Blumkin, Lubov;Lerman-Sagie, Tally;Leshinsky-Silver, Esther
遗传性痉挛截瘫(HSP)是一组以锥体束功能障碍所致的进行性肢体痉挛为主要特征的遗传性神经退行性疾病。临床上HSP分为两种类型：一种是单纯的形式，表现为进行性的肢体痉挛和无力、感觉体征和膀胱功能障碍；另一种是复杂的形式，与更广泛的神经系统和额外的神经体征以及脑成像的病理结果相关联。遗传性痉挛性截瘫伴较薄的胼胝体(HSP-TCC)是复杂性HSP的一种常见亚型，其临床特征为缓慢进行性痉挛性截瘫伴认知功能障碍，并伴有较薄的胼胝体(TCC)。SPG11是HSP-TCC最常见的相关基因，编码Spatacsin，一种功能未知的蛋白。我们描述了一个阿拉伯血缘家庭的两个兄弟姐妹，他们患有缓慢进行性痉挛性瘫痪、智力低下、癫痫、胼胝体变薄和脑室周围白质异常。纯合图谱在染色体1p13.2-1p12上发现了一个新的7.3Mb的单一候选区。AR-HSP-TCC新基因座的发现进一步证明了该病广泛的遗传异质性。(C)2011爱思唯尔B.V.保留所有权利。
The hereditary spastic paraplegias (HSP) are a heterogeneous group of genetic neurodegenerative disorders in which the main feature is progressive spasticity of the lower limbs due to pyramidal tract dysfunction. Clinically HSP are divided into two forms: a pure form that presents with progressive lower limb spasticity and weakness, sensory signs and bladder dysfunction, and a complicated form, associated with more extensive neurological and extra neurological signs as well as pathological findings on brain imaging. The clinical variability observed in HSP is supported by the large underlying genetic heterogeneity.Hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) is a frequent subtype of complicated HSP clinically characterized by a slowly progressive spastic paraparesis with cognitive impairment and thin corpus callosum (TCC). SPG11, the most frequent gene associated with HSP-TCC, encodes spatacsin, a protein of unknown function.We describe two siblings from an Arabic consanguineous family with slowly progressive spastic paraparesis, mental retardation, seizures, thin corpus callosum and periventricular white matter abnormalities. Homozygosity mapping identified a novel single candidate region of 7.3 Mb on chromosome 1p13.2-1p12. The finding of a new locus for AR-HSP-TCC further demonstrates the extensive genetic heterogeneity of this condition. (C) 2011 Elsevier B.V. All rights reserved.