Genotype-phenotype correlations in Axenfeld-Rieger malformation and glaucoma patients with FOXC1 and PITX2 mutations
Genotype-phenotype correlations in Axenfeld-Rieger malformation and glaucoma patients with FOXC1 and PITX2 mutations
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DOI：
10.1167/iovs.06-0472
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发表时间：
2007-01-01
影响因子：
4.4
通讯作者：
Walter, Michael A.
中科院分区：
文献类型：
--
作者：
Strungaru, M. Hermina;Dinu, Irina;Walter, Michael A.
目的。提高对Axenfeld-Rieger畸形（ARM）相关青光眼的认识，并确定已知FOXC1或pitx2遗传缺陷的ARM患者的最佳青光眼治疗方法。临床数据收集自诊断为ARM的患者，通过检查患者记录和使用临床问卷，我们之前在这些患者中发现了FOXC1或PITX2基因的致病突变。126例ARM患者，代表20种不同的先证者，FOXC1和PITX2改变被纳入研究。arm相关性青光眼是一种双侧前段发育不良的疾病，男女发病率相同。参与这项研究的75%的ARM患者在青春期或成年早期患有青光眼。值得注意的是，非眼部发现的患者更有可能有PITX2缺陷而不是FOXC1缺陷。只有18%的PITX2或FOXC1基因缺陷患者对药物或手术治疗（单独使用或联合使用）有反应。FOXC1突变患者青光眼发展预后最轻，而PITX2缺陷患者和FOXC1重复患者青光眼发展预后较FOXC1突变患者更为严重。在本研究中，目前的药物治疗不能成功地降低FOXC1或PITX2改变的ARM患者的眼压或防止青光眼的进展。这项临床研究也为确定导致ARM的基因提供了有用的诊断标准。
PURPOSE. To improve the understanding of Axenfeld-Rieger Malformation (ARM)-associated glaucoma and to determine the best glaucoma treatment for patients with ARM who have known genetic defects in FOXC1 or PITX2.METHODS. Clinical data were collected from patients with diagnosed ARM, in whom we had previously identified disease-causing mutations in either the FOXC1 or PITX2 genes, by examination of patient records and use of clinical questionnaires. One hundred twenty-six patients with ARM, representing 20 different probands, with FOXC1 and PITX2 alterations were included in the study.RESULTS. ARM-associated glaucoma is a bilateral anterior segment dysgenesis disease that affects males and females equally. Seventy-five percent of the patients with ARM who participated in this study had glaucoma that had developed in adolescence or early adulthood. Of note, the patients with nonocular findings were more likely to have PITX2 defects than FOXC1 defects. Glaucoma in only 18% of patients with either PITX2 or FOXC1 genetic defects responded to medical or surgical treatment (used solely or in combination).CONCLUSIONS. Patients with FOXC1 mutations have the mildest prognosis for glaucoma development, whereas patients with PITX2 defects and patients with FOXC1 duplication have a more severe prognosis for glaucoma development than do patients with FOXC1 mutations. In the present study, current medical therapies do not successfully lower intraocular pressure or prevent progression of glaucoma in patients with ARM who have FOXC1 or PITX2 alterations. This clinical study also provides useful diagnostic criteria to identify the gene responsible for ARM.