No pathogenic mutations identified in the COL8A1 and COL8A2 genes in familial Fuchs corneal dystrophy
No pathogenic mutations identified in the COL8A1 and COL8A2 genes in familial Fuchs corneal dystrophy
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DOI：
10.1167/iovs.05-1635
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发表时间：
2006-09-01
影响因子：
4.4
通讯作者：
Yellore, Vivek S.
中科院分区：
文献类型：
--
作者：
Aldave, Anthony J.;Rayner, Sylvia A.;Yellore, Vivek S.
目的.通过筛选COL8A1和COL8A2基因，研究迟发性家族性Fuchs内皮角膜营养不良（FECD）的遗传基础。COL8A1和COL8A2基因突变与早发性和迟发性、家族性和散发性FECD相关。DNA提取，PCR扩增，和COL8A1和COL8A2基因的直接测序进行了15个无关的家庭，两个或两个以上的成员与迟发性FECD。COL8A1基因的筛选没有发现来自15个FECD家族的任何受影响个体的序列变异。在COL8A2基因中，在任何受影响的患者中均未发现先前确定的在家族性FECD病例中可能起致病作用的突变（Arg155Gln，Leu450Trp和Gln455Lys）。一个以前被认为是FECD病因的突变（Arg434His）在一个被鉴定的家族中显示不与疾病分离。两个先前确定的单核苷酸多态性（SNP），Pro575Leu和Pro586Pro，分别在一个受影响的个人和三个受影响的个人（两个家庭）。先前与FECD相关的COL8A2基因中的Arg434His突变已被证明不与疾病表型分离，因此可能不被认为是致病突变。在15个家族性FECD家系的受影响成员中，在COL8A1或COL8A2基因中鉴定出的致病性突变的缺失表明其他遗传因素参与了这种常染色体显性角膜营养不良的发展。
PURPOSE. To investigate the genetic basis of late-onset, familial Fuchs endothelial corneal dystrophy ( FECD) through screening of the COL8A1 and COL8A2 genes, in which mutations have been associated with both early and late-onset, familial and sporadic FECD.METHODS. DNA extraction, PCR amplification, and direct sequencing of the COL8A1 and COL8A2 genes was performed in affected and unaffected members of 15 unrelated families with two or more members with late-onset FECD.RESULTS. Screening of the COL8A1 gene did not reveal sequence variants in any affected individuals from the 15 FECD families. In the COL8A2 gene, the previously identified mutations presumed to play a pathogenic role in cases of familial FECD ( Arg155Gln, Leu450Trp, and Gln455Lys) were not discovered in any of the affected patients. A mutation previously considered causative of FECD ( Arg434His) was shown not to segregate with the disease in the one family in which it was identified. Two previously identified single-nucleotide polymorphisms ( SNPs), Pro575Leu and Pro586Pro, were identified in a single affected individual and three affected individuals ( two families), respectively.CONCLUSIONS. The Arg434His mutation in the COL8A2 gene, previously associated with FECD, has been shown not to segregate with the disease phenotype, and thus may not be considered a disease-causing mutation. The absence of pathogenic mutations identified in the COL8A1 or COL8A2 genes in affected members of 15 pedigrees with familial FECD indicates that other genetic factors are involved in the development of this autosomal dominant corneal dystrophy.