Barbazetto Irene A, Room Miia, Yannuzzi Nicholas A, Barile Gaetano R, Merriam Joanna E, Bardal Anne M C, Freund K Bailey, Yannuzzi Lawrence A, Allikmets Rando
Department of Ophthalmology, Columbia University, New York, New York, USA.
Invest Ophthalmol Vis Sci. 2008 Sep;49(9):3806-11. doi: 10.1167/iovs.07-1357. Epub 2008 May 23.
To investigate the prevalence of sequence variants in the ATM gene and to determine the frequency of major age-related macular degeneration (AMD)-associated variants in CFH, CFB, and 10q26 loci in patients with idiopathic perifoveal telangiectasia (IPT).
Thirty patients with diagnoses of IPT underwent standard ophthalmologic evaluation that included visual acuity testing, fundus photography, and fluorescein angiography. DNA was screened for variations in the ATM gene by a combination of denaturing high-performance liquid chromatography and direct sequencing. Major AMD-associated alleles in CFH, CFB, and 10q loci were screened by PCR-restriction fragment-length polymorphism.
Nineteen female and 11 male patients (average age, 59 years) with a median visual acuity of 20/50 were evaluated. Six patients were of Asian-Indian origin, one was Hispanic, and 23 were of European-American ancestry. Nine of 30 (30%) patients had diabetes mellitus, 18 of 30 (60%) patients had hypertension, and 12 of 30 (40%) patients had a history of smoking. Screening of the ATM gene revealed a null allele in 2 of 23 (8.7%) patients of European ancestry, previously disease-associated missense alleles in 4 of 23 (17.4%) patients, and common missense alleles in 7 of 23 (30.4%) patients. No variants were identified in the ATM gene in patients of Asian or Hispanic origin. Frequencies of major AMD-associated alleles in CFH, CFB, and 10q loci in the IPT cohort were similar to those in the ethnically matched general population.
At least 26%, and maybe up to 57%, of IPT patients of European-American descent carried possibly disease-associated ATM alleles. Vascular risk factors such as hypertension, diabetes, and smoking may be associated with the pathogenesis of the disease.
研究ATM基因序列变异的患病率，并确定特发性黄斑旁毛细血管扩张症（IPT）患者中CFH、CFB和10q26位点主要年龄相关性黄斑变性（AMD）相关变异的频率。
30例诊断为IPT的患者接受了标准眼科评估，包括视力测试、眼底照相和荧光素血管造影。通过变性高效液相色谱和直接测序相结合的方法筛选DNA中ATM基因的变异。通过聚合酶链反应-限制性片段长度多态性筛选CFH、CFB和10q位点的主要AMD相关等位基因。
评估了19例女性和11例男性患者（平均年龄59岁），中位视力为20/50。6例患者为亚洲印度裔，1例为西班牙裔，23例为欧美血统。30例患者中有9例（30%）患有糖尿病，30例患者中有18例（60%）患有高血压，30例患者中有12例（40%）有吸烟史。对ATM基因的筛查显示，23例欧洲血统患者中有2例（8.7%）存在无效等位基因，23例患者中有4例（17.4%）存在先前与疾病相关的错义等位基因，23例患者中有7例（30.4%）存在常见错义等位基因。亚洲或西班牙裔患者的ATM基因未发现变异。IPT队列中CFH、CFB和10q位点主要AMD相关等位基因的频率与种族匹配的普通人群相似。
至少26%，甚至可能高达57%的欧美血统IPT患者携带可能与疾病相关的ATM等位基因。高血压、糖尿病和吸烟等血管危险因素可能与该疾病的发病机制有关。
