PAX6 mutations: genotype-phenotype correlations.
PAX6 mutations: genotype-phenotype correlations.
复制标题
PAX6突变：基因型 - 表型相关性。
DOI：
10.1186/1471-2156-6-27
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发表时间：
2005-05-26
期刊：
影响因子：
2.9
通讯作者：
Hanson, IM
中科院分区：
文献类型：
--
作者：
Tzoulaki, I;White, IMS;Hanson, IM
PAX6蛋白是一种高度保守的转录调节因子，对正常的眼睛和神经发育非常重要。在人类中，PAX6基因的杂合突变会导致无虹膜(虹膜缺失)和相关的发育性眼病。Pax6突变被存档在人类PAX6等位基因变异数据库中，该数据库目前包含309条记录，其中286条是眼睛畸形患者的突变。我们检查了人类PAX6等位基因变异数据库中的记录，记录了不同突变类型的频率，与不同突变类型相关的表型，CpG转变对PAX6突变谱的贡献，以及链终止突变在开放阅读框中的分布。将提前终止密码子引入开放阅读框架的突变主要与无虹膜有关；相比之下，非无虹膜表型通常与错义突变有关。外显子8、9、10和11上的4个CpG二核苷酸是主要的突变热点，这些CpG上的转换占数据库中所有无义突变的一半以上。截短突变分布在整个PAX6编码区，除了外显子12的后半部分和外显子13的编码部分，它们完全不存在。编码区3‘端没有截断突变具有统计学意义，这与无义介导的衰变作用于PAX6突变等位基因的观点是一致的。PAX6等位基因变异数据库是研究基因-表型相关性的宝贵资源。截断突变与无虹膜表型的一致关联，以及PAX6开放阅读框中截断突变的分布，表明无义介导的衰变作用于PAX6突变等位基因。
The PAX6 protein is a highly conserved transcriptional regulator that is important for normal ocular and neural development. In humans, heterozygous mutations of the PAX6 gene cause aniridia (absence of the iris) and related developmental eye diseases. PAX6 mutations are archived in the Human PAX6 Allelic Variant Database, which currently contains 309 records, 286 of which are mutations in patients with eye malformations. We examined the records in the Human PAX6 Allelic Variant Database and documented the frequency of different mutation types, the phenotypes associated with different mutation types, the contribution of CpG transitions to the PAX6 mutation spectrum, and the distribution of chain-terminating mutations in the open reading frame. Mutations that introduce a premature termination codon into the open reading frame are predominantly associated with aniridia; in contrast, non-aniridia phenotypes are typically associated with missense mutations. Four CpG dinucleotides in exons 8, 9, 10 and 11 are major mutation hotspots, and transitions at these CpG's account for over half of all nonsense mutations in the database. Truncating mutations are distributed throughout the PAX6 coding region, except for the last half of exon 12 and the coding part of exon 13, where they are completely absent. The absence of truncating mutations in the 3' part of the coding region is statistically significant and is consistent with the idea that nonsense-mediated decay acts on PAX6 mutant alleles. The PAX6 Allelic Variant Database is a valuable resource for studying genotype-phenotype correlations. The consistent association of truncating mutations with the aniridia phenotype, and the distribution of truncating mutations in the PAX6 open reading frame, suggests that nonsense-mediated decay acts on PAX6 mutant alleles.
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影响因子：
3.9
作者：
Chao, LY;Mishra, R;Saunders, GF
通讯作者：
Saunders, GF
影响因子：
0.9
作者：
Heyman, I;Frampton, I;Simonoff, E
通讯作者：
Simonoff, E
影响因子：
30.8
作者：
JORDAN, T;HANSON, I;VANHEYNINGEN, V
通讯作者：
VANHEYNINGEN, V
影响因子：
9.8
作者：
Azuma, N;Yamaguchi, Y;Yamada, M
通讯作者：
Yamada, M
影响因子：
11.2
作者：
Mitchell, TN;Free, SL;Sisodiya, SM
通讯作者：
Sisodiya, SM