Posterior column ataxia with retinitis pigmentosa in a Japanese family with a novel mutation in FLVCR1
Posterior column ataxia with retinitis pigmentosa in a Japanese family with a novel mutation in FLVCR1
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DOI：
10.1007/s10048-010-0271-4
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发表时间：
2011-05-01
期刊：
影响因子：
2.2
通讯作者：
Tsuji, Shoji
中科院分区：
文献类型：
--
作者：
Ishiura, Hiroyuki;Fukuda, Yoko;Tsuji, Shoji
后柱共济失调伴视网膜色素变性（PCARP）是一种常染色体隐性遗传神经退行性疾病，其特征为视网膜色素变性和感觉性共济失调。先前对两个家族的 PCARP 研究表明与 1q31-q32 存在关联。然而，对 PCARP 的临床表现和分子遗传学的详细研究仍然有限。在这里，我们描述一个具有 PCARP 的日本近亲家庭。两个受影响的兄弟姐妹患有儿童期发病的视网膜色素变性和缓慢进展的感觉共济失调。他们还表现出轻度智力低下，而 PCARP 患者中尚未描述过这种情况。使用高密度单核苷酸多态性阵列的参数连锁分析支持与相同基因座的连锁。目标捕获和高通量测序技术揭示了 FLVCR1 中的一种新的纯合 c.1477G > C (G493R) 突变，该突变与该疾病共分离。最近的一项研究在原始家族和其他家族中发现了 FLVCR1 的三个独立突变。我们的结果进一步证实PCARP是由FLVCR1突变引起的。
Posterior column ataxia with retinitis pigmentosa (PCARP) is an autosomal recessive neurodegenerative disorder characterized by retinitis pigmentosa and sensory ataxia. Previous studies of PCARP in two families showed a linkage to 1q31-q32. However, detailed investigations on the clinical presentations as well as molecular genetics of PCARP have been limited. Here, we describe a Japanese consanguineous family with PCARP. Two affected siblings suffered from childhood-onset retinitis pigmentosa and slowly progressive sensory ataxia. They also showed mild mental retardation, which has not been described in patients with PCARP. Parametric linkage analysis using high-density single nucleotide polymorphism arrays supported a linkage to the same locus. Target capture and high-throughput sequencing technologies revealed a novel homozygous c.1477G > C (G493R) mutation in FLVCR1, which cosegregated with the disease. A recent study has identified three independent mutations in FLVCR1 in the original and other families. Our results further confirmed that PCARP is caused by mutations in FLVCR1.