Missense mutations in the DNA-binding region and termination codon in PAX6
Missense mutations in the DNA-binding region and termination codon in PAX6
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DOI：
10.1002/humu.10163
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发表时间：
2003-02-01
期刊：
影响因子：
3.9
通讯作者：
Saunders, GF
中科院分区：
文献类型：
--
作者：
Chao, LY;Mishra, R;Saunders, GF
我们在30名无虹膜患者中发现了PAX 6基因的9种新型基因内突变。1例肾母细胞瘤、无虹膜、泌尿生殖系统异常和智力低下（WAGR综合征）患者有11 p缺失，并失去了父亲的PAX6等位基因。两名患者有小的缺失：一个移码应导致PAX6蛋白的早期终止，另一个移码导致终止位点改变并进入3 '非翻译区（UTR）。其他27名患者有单碱基对突变。4个存在拼接缺陷; 3例IVS6 + 1G> A，位于PAX6基因突变热点; 10例提前终止（4例1024C> T [R203X]，也位于突变热点）; 6例错义突变。错义突变A321T（1378G> A）为多态性改变，其他5个错义突变为L46R、C52R、I56T、G73D和I87K。这五个密码子位于PAX6配对结构域中，并且在整个配对家族中高度保守。7例患者在正常终止密码子（TAA）中发生突变。这种变化导致运行进入3'UTR，并且也处于突变热点。所有30个突变都应导致PAX6单倍不足。未观察到突变位点与表型之间的相关性。
We have identified nine novel intragenic mutations of the PAX6 gene in 30 patients with aniridia. One patient with Wilms' tumor, aniridia, genitourinary anomalies, and mental retardation (WAGR syndrome) had deletion of 11p and had lost the paternal PAX6 allele. Two patients had small deletions: a frameshift that should result in early termination of the PAX6 protein, and a frameshift that leads to a terminatio-nsite change and run-on into the 3' untranslated region (UTR). The other 27 patients had single base-pair mutations. Four had splicing defects; three had IVS6+1G>A, which was at a mutation hotspot in the PAX6 gene; 10 had premature termination (four 1024C>T [R203X], also at a mutation hotspot); and six had missense mutations. Missense mutation A321T (1378G>A) was a polymorphic change; the other five missense mutations were L46R, C52R, I56T, G73D, and I87K. These five codons are in the PAX6 paired domain and are highly conserved throughout the entire paired family. Seven patients had a mutation in the normal stop codon (TAA). This change leads to run,on into the 3' UTR and is also at a mutation hotspot. All 30 mutations should result in PAX6 haploinsufficiency. No correlation was observed between mutation sites and phenotypes.