Spastic Paraplegia, Optic Atrophy, and Neuropathy: New Observations, Locus Refinement, and Exclusion of Candidate Genes
Spastic Paraplegia, Optic Atrophy, and Neuropathy: New Observations, Locus Refinement, and Exclusion of Candidate Genes
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DOI：
10.1111/j.1469-1809.2009.00507.x
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发表时间：
2009-05-01
影响因子：
1.9
通讯作者：
Zatz, Mayana
中科院分区：
文献类型：
--
作者：
Macedo-Souza, Lucia Ines;Kok, Fernando;Zatz, Mayana
SPOAN是一种常染色体隐性遗传性神经退行性疾病，其特征在于最近由我们的小组在一个大型巴西近亲繁殖家庭中有25个受影响的个体。这种情况在临床上定义为：1。先天性视神经萎缩; 2.婴儿期发作的进行性痉挛性截瘫; 3.进行性运动和感觉轴突神经病。总的来说，我们现在知道68例SPOAN患者（45例女性和23例男性，年龄从5岁到72岁不等），其中44例是首次在这里介绍。他们都出生在同一个地理小区域。这68名患者属于43个兄弟姐妹，其中40人表现出父母的血缘关系。61名患者接受了全面的临床评估，64名患者被纳入遗传学调查。所有分子研究的患者都是11q13处D11S1889的纯合子。这使我们能够将SPOAN基因的关键区域从4.8 Mb减少到2.3 Mb，最大两点lod得分为33.2（标记D11S987）和27.0（标记D11S1889）。位于这个新定义的关键区域的三个基因进行测序，但没有检测到致病性突变。负责SPOAN的基因仍然难以捉摸。
SPOAN is an autosomal recessive neurodegenerative disorder which was recently characterized by our group in a large inbred Brazilian family with 25 affected individuals. This condition is clinically defined by: 1. congenital optic atrophy; 2. progressive spastic paraplegia with onset in infancy; and 3. progressive motor and sensory axonal neuropathy. Overall, we are now aware of 68 SPOAN patients (45 females and 23 males, with age ranging from 5 to 72 years), 44 of which are presented here for the first time. They were all born in the same geographic micro region. Those 68 patients belong to 43 sibships, 40 of which exhibit parental consanguinity. Sixty-one patients were fully clinically evaluated and 64 were included in the genetic investigation. All molecularly studied patients are homozygotes for D11S1889 at 11q13. This enabled us to reduce the critical region for the SPOAN gene from 4.8 to 2.3 Mb, with a maximum two point lod score of 33.2 (with marker D11S987) and of 27.0 (with marker D11S1889). Three genes located in this newly defined critical region were sequenced, but no pathogenic mutation was detected. The gene responsible for SPOAN remains elusive.