A locus for autosomal dominant keratoconus: linkage to 16q22.3-q23.1 in Finnish families.
A locus for autosomal dominant keratoconus: linkage to 16q22.3-q23.1 in Finnish families.
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发表时间：
2002-10
影响因子：
4.4
通讯作者：
H. Tyynismaa;P. Sistonen;S. Tuupanen;T. Tervo;A. Dammert;T. Latvala;T. Alitalo
中科院分区：
文献类型：
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作者：
H. Tyynismaa;P. Sistonen;S. Tuupanen;T. Tervo;A. Dammert;T. Latvala;T. Alitalo
圆锥角膜的全球患病率估计为50 - 230/100，000。散发性圆锥角膜是西方国家角膜移植手术的主要原因。阳性家族史在6%至8%的患者中报告。本研究的目的是绘制20个芬兰常染色体显性圆锥角膜家族的疾病位点，每个家族有两个或更多的受影响的成员，没有其他相关的遗传疾病。方法从42名患者和34名正常人的血样中提取DNA。对患者及其父母的基因组DNA进行292个多态性标记的等位基因分型。进行全基因组筛选以定位疾病基因。通过聚合酶链反应扩增荧光标记物，并在自动测序仪上分离。将等位基因大小分配给每个家庭成员，然后计算LOD评分。结果该疾病位点定位于染色体16 q，位于标记D16 S2624和D16 S3090之间，最大参数多点LOD评分为4.10，相应的非参数评分为3.27（NPL，P = 0.00006）。来自20个家庭的证据提供了支持的连锁，符合一个单一的基因座家族性常染色体显性圆锥角膜没有异质性。结论：本研究是首次对圆锥角膜进行全基因组连锁定位的研究。结果提示圆锥角膜致病基因位于16q22.3-q23.1染色体区域。
PURPOSE The estimated world-wide prevalence of keratoconus is 50 to 230 per 100,000 in the general population. Sporadic keratoconus is the leading cause of corneal transplantation surgery in Western countries. Positive family history has been reported in 6% to 8% of patients. The purpose of this study was to map the disease locus in 20 Finnish families with autosomal dominant keratoconus, each family having two or more affected members and with no other associated genetic disease. METHODS DNA was extracted from blood samples, collected from 42 affected and 34 unaffected family members. Genomic DNA from patients and their parents, was typed for alleles of 292 polymorphic markers. A genome-wide screening was performed to localize the disease gene. Fluorescent markers were amplified by polymerase chain reaction and separated on an automated sequencer. Allele sizes were assigned to each family member, after which LOD scores were calculated. RESULTS The disease locus was mapped to chromosome 16q, between the markers D16S2624 and D16S3090, with a maximum parametric multipoint LOD score of 4.10 and corresponding nonparametric score of 3.27 (NPL, P = 0.00006). Evidence from 20 families provided support for the linkage, consistent with a single locus for familial autosomal dominant keratoconus without heterogeneity. CONCLUSIONS This study is the first genome-wide linkage study to map the keratoconus gene. The results suggest that the causative gene in keratoconus is located within the 16q22.3-q23.1 chromosomal region.