A compound heterozygous change found in Peters' anomaly.
A compound heterozygous change found in Peters' anomaly.
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DOI：
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发表时间：
2005-01
期刊：
影响因子：
2.2
通讯作者：
A. Churchill;A. Yeung
中科院分区：
文献类型：
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作者：
A. Churchill;A. Yeung
目的确定先天性青光眼基因CYP 1B 1的序列变异是否存在于Peters异常个体中，Peters异常是一种常与青光眼相关的发育性眼异常。方法应用核酸片段分析系统对26例Peters畸形患者（9例家族性，17例单纯性）的CYP 1B 1基因编码区进行异源双链分析。通过测序确定与野生型模式的偏差。结果6个核苷酸位点与野生型不同。其中4个先前在临床正常个体中观察到：-13在间插序列1（IVS 1），密码子48、432和449中。我们在一个受影响的个体中发现了IVS 1中-16处的新序列变异。在我们26例Peters异常的非亲缘病例中，有6例在432密码子处观察到一种新的复合杂合子模式。结论首次报道Peters异常中存在2种新的CYP 1B 1序列变异。-16 IVS 1变化在编码区之外，可能是一种罕见的多态性。密码子432处的复合杂合变化在编码区的保守部分内，并且用亮氨酸或精氨酸取代缬氨酸。在100名正常对照中未观察到这种变化。此外，我们提出了这一发现如何影响蛋白质功能。
PURPOSE To determine whether sequence variations in the congenital glaucoma gene, CYP1B1, are present in individuals with Peters' anomaly, a developmental eye anomaly frequently associated with glaucoma. METHODS The CYP1B1 coding region was screened in 26 individuals with Peters' anomaly (9 familial and 17 simplex cases) by heteroduplex analysis using the Transgenomic Wave nucleic acid fragment analysis system. Deviations from the wild type pattern were determined by sequencing. RESULTS Six nucleotide positions varied from the wild type. Four of these have previously been observed in clinically normal individuals: -13 in intervening sequence 1 (IVS1), codons 48, 432, and 449. We found a novel sequence variation at -16 in IVS1 in one affected individual. A novel compound heterozygote pattern was observed at codon 432 in 6 of our 26 unrelated cases with Peters' anomaly. CONCLUSIONS This is the first report of 2 novel CYP1B1 sequence variations seen in Peters' anomaly. The -16 IVS1 change is outside the coding region and likely to be a rare polymorphism. The compound heterozygous change at codon 432 is within a conserved part of the coding region and substitutes valine with either leucine or arginine. This change has not been observed in 100 normal controls. Furthermore, we propose how this finding may affect protein function.