PAX6 gene variations associated with aniridia in south India.
PAX6 gene variations associated with aniridia in south India.
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DOI：
10.1186/1471-2350-5-9
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发表时间：
2004-04-16
影响因子：
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通讯作者：
Sundaresan P
中科院分区：
文献类型：
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作者：
Neethirajan G;Krishnadas SR;Vijayalakshmi P;Shashikant S;Sundaresan P
转录因子基因 PAX6 的突变已被证明是无虹膜表型的原因。本研究的目的是分析无虹膜患者，以揭示南印度人群中的 PAX6 基因突变。从 6 个临床诊断无虹膜家族的 28 名成员和 60 名正常健康对照的外周血中分离出总基因组 DNA。通过 PCR 扩增人类 PAX6 基因的编码外显子，并通过单链构象多态性 (SSCP) 检测等位基因特异性变异，然后进行自动测序。测序结果揭示了三名散发性无虹膜患者的新 PAX6 突变：c.715ins5、[c.1201delA； c.1239A>G]和c.901delA。还发现了两个先前报道的无义突变：c.482C>A、c.830G>A。在内含子9和外显子10边界处检测到中性多态性(IVS9-12C>T)。人类PAX6基因编码区发现的两个无义突变在南印度人群中首次报道。遗传分析证实 PAX6 基因的单倍体不足导致了经典的无虹膜表型。我们研究中检测到的大多数点突变都会产生终止密码子。在这里，我们将南印度人群中的三个新的 PAX6 基因突变添加到现有的突变谱中，这并不是一个经过充分研究的种族群体。我们的研究支持 PAX6 基因突变与无虹膜表达相关的假设。
Mutations in the transcription factor gene PAX6 have been shown to be the cause of the aniridia phenotype. The purpose of this study was to analyze patients with aniridia to uncover PAX6 gene mutations in south Indian population. Total genomic DNA was isolated from peripheral blood of twenty-eight members of six clinically diagnosed aniridia families and 60 normal healthy controls. The coding exons of the human PAX6 gene were amplified by PCR and allele specific variations were detected by single strand conformation polymorphism (SSCP) followed by automated sequencing. The sequencing results revealed novel PAX6 mutations in three patients with sporadic aniridia: c.715ins5, [c.1201delA; c.1239A>G] and c.901delA. Two previously reported nonsense mutations were also found: c.482C>A, c.830G>A. A neutral polymorphism was detected (IVS9-12C>T) at the boundary of intron 9 and exon 10. The two nonsense mutations found in the coding region of human PAX6 gene are reported for the first time in the south Indian population. The genetic analysis confirms that haploinsuffiency of the PAX6 gene causes the classic aniridia phenotype. Most of the point mutations detected in our study results in stop codons. Here we add three novel PAX6 gene mutations in south Indian population to the existing spectrum of mutations, which is not a well-studied ethnic group. Our study supports the hypothesis that a mutation in the PAX6 gene correlates with expression of aniridia.