Replication and refinement of linkage of posterior polymorphous corneal dystrophy to the posterior polymorphous corneal dystrophy 1 locus on chromosome 20
Replication and refinement of linkage of posterior polymorphous corneal dystrophy to the posterior polymorphous corneal dystrophy 1 locus on chromosome 20
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DOI：
10.1097/gim.0b013e31803c4dc2
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发表时间：
2007-04-01
影响因子：
8.8
通讯作者：
Aldave, Anthony J.
中科院分区：
文献类型：
--
作者：
Yellore, Vivek S.;Papp, Jeanette C.;Aldave, Anthony J.
目的：本研究的目的是确定后部多形角膜营养不良的遗传基础，这是一种常染色体显性遗传的角膜内皮疾病，与角膜水肿的发展有关，需要角膜移植进行视力康复。青光眼也发生在多达40%的后部多形性角膜营养不良患者中。研究方法：连锁分析，使用微卫星标记先前用于证明连锁的后部多形角膜营养不良的20号染色体的候选区域称为后部多形角膜营养不良1，进行了29个成员的一个家庭与后部多形角膜营养不良。34个微卫星标记用于细化后多形性角膜营养不良1间隔。TCF 8位于10号染色体上，在受影响的家族成员中进行筛查，以排除后部多形性角膜营养不良3。结果如下：通过单点和多点分析，获得了与后部多形性角膜营养不良1间隔相关的重要证据。在标记D20 S471处获得的最大单点对数优势比得分为4.38（θ = 0）;在D20 S471的4.7 Mbp（7.2 cM）内，8个标记提供的单点对数优势比得分大于3.00，3个标记提供的单点对数优势比得分大于4.00。获得的最大多点对数比值比评分为4.83，发现相邻标记D20 S844、D20 S191、D20 S484和D20 S111。我们报告的家族中后部多形性角膜营养不良1的支持间隔约为13.5 Mbp（10 cM）长，位于标记D20 S182和D20 S195之间。11个标记物在该区域内具有大于4.0的多点对数比值比得分。在一个受影响的家族成员中没有发现TCF 8编码区突变，有效地排除了后部多形性角膜营养不良3。结论：最初描述的19.8 cM后部多形性角膜营养不良1候选疾病间隔已被细化为标记D20 S182和D20 S195之间的10 cM间隔。这个细化区间的一部分与最近报道的后部多形性角膜营养不良1区间重叠，只有20个已知和预测的基因映射到2.4 cM的共同区间。
Purpose: The study purpose was to identify the genetic basis of posterior polymorphous corneal dystrophy, an autosomal dominant disorder of the corneal endothelium that is associated with the development of corneal edema, necessitating corneal transplantation for visual rehabilitation. Glaucoma also develops in up to 40% of patients with posterior polymorphous corneal dystrophy. Methods: Linkage analysis, using microsatellite markers previously used to demonstrate linkage of posterior polymorphous corneal dystrophy to the chromosome 20 candidate region known as posterior polymorphous corneal dystrophy 1, was performed in 29 members of a family with posterior polymorphous corneal dystrophy. Thirty-four microsatellite markers were used to refine the posterior polymorphous corneal dystrophy 1 interval. TCF8, located on chromosome 10, was screened in an affected family member to exclude posterior polymorphous corneal dystrophy 3. Results: Significant evidence of linkage to the posterior polymorphous corneal dystrophy 1 interval was obtained with both single-point and multipoint analyses. The largest single-point log odds ratio score obtained was 4.38 (theta = 0) at marker D20S471; within 4.7 Mbp (7.2 cM) of D20S471 eight markers provided single-point log odds ratio scores of greater than 3.00 and three markers provided single-point log odds ratio scores greater than 4.00. The largest multipoint log odds ratio score obtained was 4.83, found across the adjacent markers D20S844, D20S191, D20S484, and D20S111. The support interval for posterior polymorphous corneal dystrophy 1 in the family we report is approximately 13.5 Mbp (10 cM) long and lies between the markers D20S182 and D20S195. Eleven markers have multipoint log odds ratio scores greater than 4.0 within this region. No coding region mutations were identified in TCF8 in an affected member of the family, effectively excluding posterior polymorphous corneal dystrophy 3. Conclusions: The originally described 19.8 cM posterior polymorphous corneal dystrophy 1 candidate disease interval has been refined to a 10 cM interval between markers D20S182 and D20S195. A portion of this refined interval overlaps a more recently reported posterior polymorphous corneal dystrophy 1 interval, with only 20 known and predicted genes mapped to the 2.4 cM common interval.