Mutations in a new photoreceptor-pineal gene on 17p cause Leber congenital amaurosis
Mutations in a new photoreceptor-pineal gene on 17p cause Leber congenital amaurosis
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DOI：
10.1038/71732
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发表时间：
2000-01-01
期刊：
影响因子：
30.8
通讯作者：
Daiger, SP
中科院分区：
文献类型：
--
作者：
Sohocki, MM;Bowne, SJ;Daiger, SP
Leber先天性黑色素(LCA，MIM 204000)至少占所有遗传性视网膜疾病的5%(1)，是发病年龄最早的最严重的遗传性视网膜病变(2)。LCA患者在出生时或出生后头几个月被诊断为视力严重受损或失明、眼球震颤和视网膜电图(ERG)异常或平坦。GUCY2D基因突变(参考文献3)，RPE65(参考文献4)和CRX(参考文献5)是已知的导致LCA的基因，但一项研究发现，在LCA基因座映射到17p13.1(参考文献)的15个家系中，只有8个GUCY2D突变导致疾病。3)，提示另一个LCA基因座可能位于17p13.1。为了证实这一预测，一个巴基斯坦家庭的LCA被定位到17p13.1，介于D17S849和D17S960之间--一个不包括GUCY2D的区域。该家族中的LCA已被指定为LCA4(参考文献6)。我们在这里描述了一个新的光感受器/松果体表达基因AIPL1(编码芳烃相互作用蛋白样1)，它位于LCA4候选区，其蛋白含有三个四肽(TPR)基序，与核运输或伴侣活性一致。在最初的LCA4家族中，所有受影响的成员都存在278密码子的纯合子无义突变。AIPL1突变可能导致大约20%的隐性LCA，因为在14个LCA家系中有3个发现了致病突变，这些突变以前没有进行过连锁检测。
Leber congenital amaurosis (LCA, MIM 204000) accounts for at least 5% of all inherited retinal disease(1) and is the most severe inherited retinopathy with the earliest age of onset(2). Individuals affected with LCA are diagnosed at birth or in the first few months of life with severely impaired vision or blindness, nystagmus and an abnormal or flat electroretinogram (ERG). Mutations in GUCY2D (ref. 3), RPE65 (ref. 4) and CRX (ref. 5) are known to cause LCA, but one study identified disease-causing GUCY2D mutations in only 8 of 15 families whose LCA locus maps to 17p13.1 (ref. 3), suggesting another LCA locus might be located on 17p13.1. Confirming this prediction, the LCA in one Pakistani family mapped to 17p13.1, between D17S849 and D17S960-a region that excludes GUCY2D. The LCA in this family has been designated LCA4 (ref. 6). We describe here a new photoreceptor/pineal-expressed gene, AIPL1 (encoding aryl-hydrocarbon interacting protein-like 1), that maps within the LCA4 candidate region and whose protein contains three tetratricopeptide (TPR) motifs, consistent with nuclear transport or chaperone activity. A homozygous nonsense mutation at codon 278 is present in all affected members of the original LCA4 family. AIPL1 mutations may cause approximately 20% of recessive LCA, as disease-causing mutations were identified in 3 of 14 LCA families not tested previously for linkage.