Null RPGRIP1 alleles in patients with Leber congenital amaurosis
Null RPGRIP1 alleles in patients with Leber congenital amaurosis
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DOI：
10.1086/320113
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发表时间：
2001-05-01
影响因子：
9.8
通讯作者：
Berson, EL
中科院分区：
文献类型：
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作者：
Dryja, TP;Adams, SM;Berson, EL
我们分离并鉴定了编码与RPGR相互作用的蛋白质的人类基因的整个编码序列，RPGR是一种在许多X连锁视网膜色素变性病例中不存在或突变的蛋白质。新发现的基因RPGRIP1是RPGR相互作用蛋白（MIM 605446），位于14q11，它编码一个预计含有1259个氨基酸的蛋白质。先前发表的工作表明，这两种蛋白质，RPGR和RPGRIP1，存在于连接杆和锥光感受器的内外段的纤毛结构中。我们调查了57例无亲缘关系的先天性莱伯黑蒙患者的RPGRIP1突变，发现3例（6%）患者的RPGRIP1等位基因均存在隐性突变。这些突变都产生了提前终止密码子，很可能是无效等位基因。RPGRIP1突变患者的视杆细胞和视锥细胞均发生变性，并且在生命早期，他们会经历严重的中枢敏锐度丧失，从而导致眼球震颤。
We isolated and characterized the entire coding sequence of a human gene encoding a protein that interacts with RPGR, a protein that is absent or mutant in many cases of X-linked retinitis pigmentosa. The newly identified gene, called "RPGRIP1" for RPGR-interacting protein (MIM 605446), is located within 14q11, and it encodes a protein predicted to contain 1, 259 amino acids. Previously published work showed that both proteins, RPGR and RPGRIP1, are present in the ciliary structure that connects the inner and outer segments of rod and cone photoreceptors. We surveyed 57 unrelated patients who had Leber congenital amaurosis for mutations in RPGRIP1 and found recessive mutations involving both RPGRIP1 alleles in 3 (6%) patients. The mutations all create premature termination codons and are likely to be null alleles. Patients with RPGRIP1 mutations have a degeneration of both rod and cone photoreceptors, and, early in life, they experience a severe loss of central acuity, which leads to nystagmus.