Novel and De-novo Truncating PAX6 Mutations and Ocular Phenotypes in Thai Aniridia Patients
Novel and De-novo Truncating PAX6 Mutations and Ocular Phenotypes in Thai Aniridia Patients
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DOI：
10.1080/13816810500481667
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发表时间：
2006-01
影响因子：
1.2
通讯作者：
L. Atchaneeyasakul;A. Trinavarat;D. Dulayajinda;Kornphet Kumpornsin;W. Thongnoppakhun;P. Yenchitsomanus;C. Limwongse
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文献类型：
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作者：
L. Atchaneeyasakul;A. Trinavarat;D. Dulayajinda;Kornphet Kumpornsin;W. Thongnoppakhun;P. Yenchitsomanus;C. Limwongse
目的：描述泰国无虹膜患者的眼科表现和PAX 6基因突变分析。方法：对来自6个无血缘关系家系的10例患者进行全面的眼科检查。通过单链构象多态性（SSCP）和SSCP变体的直接DNA测序来筛选PAX 6基因中的突变。结果：7例患者发生白内障，6例发生青光眼。突变分析表明，四个不同的截断突变，其中两个是从头。这些包括一个新的插入/缺失突变（c.474del12insGA在外显子5）和三个无义突变。R203 X和R240 X是常见的复发性突变，而外显子10的Q277 X是新突变。所有突变都导致PAX 6蛋白功能丧失。结论：我们的数据证实了家族间和家族内可变的表型表现，其潜在机制可能是单倍不足或显性阴性突变。
Purpose: To describe the ophthalmic findings and mutation analyses of the PAX6 gene in Thai aniridia patients. Methods: Ten patients from six unrelated families underwent a comprehensive ophthalmic examination. Mutations in the PAX6 gene were screened by single-strand conformational polymorphism (SSCP) and direct DNA sequencing of the SSCP variants. Results: Seven patients developed cataracts and six developed glaucoma. Mutation analysis demonstrated four different truncating mutations, two of which were de novo. These included one novel insertion/deletion mutation (c.474del12insGA in exon 5) and three nonsense mutations. R203X and R240X are common recurrent mutations, while Q277X in exon 10 is novel. All mutations resulted in loss of function of the PAX6 protein. Conclusion: Our data confirm inter- and intrafamilial variable phenotypic manifestations of which the underlying mechanisms may be haploinsufficiency or dominant-negative mutation.