Ozgül R K, Bozkurt B, Kiratli H, Oğüş A
Department of Molecular Biology, Hacettepe University, Ankara, Turkey.
Eye (Lond). 2006 Jul;20(7):817-9. doi: 10.1038/sj.eye.6702024. Epub 2005 Aug 5.
Leber's congenital amaurosis (LCA) is an inherited retinal dystrophy, which causes severe visual impairment in early childhood. Recent molecular genetic studies have linked 11 loci (AIPL1, CRB1, CRX, GUCY2D, RPE65, RDH12, RPGRIP1, TULP1, LCA3, LCA5, and LCA9) to LCA. LCA5 is a new locus, which maps to the 6q11-q16 chromosomal region and was found to be associated with macular coloboma-type LCA in a Pakistani family. Herein, we describe the molecular genetic features of a consanguineous Turkish family in which four children have macular coloboma-type LCA.
Haplotype analysis was performed on the DNA of the family members using microsatellite markers against GUCY2D, RPE65, and LCA5. Genomic DNA was screened for mutations by means of single-strand conformational polymorphism (SSCP) analysis in exons of the RPE65 and CRX genes.
In haplotype analysis, no linkage to LCA5 or GUCY2D loci was detected. None of the tested markers showed homozygosity or segregation between affected siblings. PCR-SSCP mutation analysis revealed no mutations in the screened RPE65 and CRX genes.
We excluded LCA5 as the genetic cause of macular coloboma-type LCA in this Turkish family. Macular coloboma-type LCA shows genetic heterogeneity and it is not possible to establish a phenotype-genotype correlation with LCA5 and macular coloboma.
莱伯先天性黑蒙（LCA）是一种遗传性视网膜营养不良，可导致儿童早期严重视力损害。最近的分子遗传学研究已将11个基因座（AIPL1、CRB1、CRX、GUCY2D、RPE65、RDH12、RPGRIP1、TULP1、LCA3、LCA5和LCA9）与LCA相关联。LCA5是一个新的基因座，定位于6q11 - q16染色体区域，在一个巴基斯坦家族中发现它与黄斑缺损型LCA相关。在此，我们描述了一个近亲结婚的土耳其家族的分子遗传学特征，该家族中有4名儿童患有黄斑缺损型LCA。
使用针对GUCY2D、RPE65和LCA5的微卫星标记对家族成员的DNA进行单倍型分析。通过单链构象多态性（SSCP）分析对RPE65和CRX基因的外显子进行基因组DNA突变筛查。
在单倍型分析中，未检测到与LCA5或GUCY2D基因座的连锁。所检测的标记均未显示纯合性或在患病同胞之间的分离。PCR - SSCP突变分析显示在筛查的RPE65和CRX基因中未发现突变。
我们排除了LCA5作为这个土耳其家族中黄斑缺损型LCA的遗传病因。黄斑缺损型LCA表现出遗传异质性，无法建立LCA与LCA5及黄斑缺损之间的表型 - 基因型相关性。
