Spastic paraplegia, optic atrophy, and neuropathy is linked to chromosome 11q13
Spastic paraplegia, optic atrophy, and neuropathy is linked to chromosome 11q13
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DOI：
10.1002/ana.20478
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发表时间：
2005-05-01
影响因子：
11.2
通讯作者：
Zatz, M
中科院分区：
文献类型：
--
作者：
Macedo-Souza, LI;Kok, F;Zatz, M
我们报告了一个巴西近亲繁殖大家庭的25名白人成员的常染色体隐性遗传性神经退行性疾病，其中22人进行了临床评估。这种情况的特征是：(1)继发于明显的非进行性先天性视神经萎缩的视力不正常；(2)婴儿期起病的进行性痉挛截瘫；(3)儿童末期/青春期起病的进行性运动和感觉性轴索神经病；(4)从第三个十年开始的构音障碍；(5)加重的听觉惊吓反应；(6)进行性关节痉挛和脊柱畸形。运动障碍严重，所有患者15岁以后都被绑在轮椅上。我们进行了全基因组筛查，包括25个受影响的个体和49个未受影响的亲属。利用标记D11S1883，在11q13区域检测到连锁，其优势分数的最大对数为+14.43。该候选区域位于D11S1908和D11S1889之间，包含类似4.8Mb的区域，有100多个基因和表达序列。我们建议缩写为SPOAN(痉挛性截瘫、视神经萎缩和神经病)来治疗这种复杂的综合征。
We report an autosomal recessive neurodegenerative disorder in 25 white members from a large inbred Brazilian family, 22 of whom were evaluated clinically. This condition is characterized by (1) subnormal vision secondary to apparently nonprogressive congenital optic atrophy; (2) onset of progressive spastic paraplegia in infancy; (3) onset of progressive motor and sensory axonal neuropathy in late childhood/early adolescence; (4) dysarthria starting in the third decade of life; (5) exacerbated acoustic startle response; and (6) progressive joint contractures and spine deformities. Motor handicap was severe, and all patients were wheelchair bound after 15 years old. We performed a genome-wide screen including 25 affected individuals and 49 of their unaffected relatives. Linkage was detected at 11q13 region with a maximum logarithm of odds score of +14.43, obtained with marker D11S1883. The candidate region, which lies between D11S1908 and D11S1889, encompasses similar to 4.8Mb and has more than 100 genes and expressed sequences. We propose the acronym SPOAN (spastic paraplegia, optic atrophy, and neuropathy) for this complex syndrome.