Weigell-Weber Maike, Sarra Gian-Marco, Kotzot Dieter, Sandkuijl Lodewijk, Messmer Elmar, Hergersberg Martin
Institute of Medical Genetics, University of Zurich, Switzerland.
Arch Ophthalmol. 2003 Aug;121(8):1184-8. doi: 10.1001/archopht.121.8.1184.
To localize the gene that causes an autosomal recessively inherited vitreoretinal dystrophy that has not been described, to our knowledge, and to analyze a candidate gene mapped to 22q13 (fibulin-1 [FBLN1]).
Homozygosity mapping with 500 microsatellite markers spread over the whole genome (mean distance, 7.2 centimorgans [cM]) and mutation analysis of the complete coding region of FBLN1.
Homozygosity for all analyzed markers was found in the 4 affected siblings in a region on chromosome 22 encompassing 12 cM from D22S444 (centromeric) to D22S1170 (telomeric). Lod scores were between 0.017 and 2.36 (theta = 0). A mutation analysis of the complete coding region of FBLN1, which encodes interacting extracellular matrix proteins, revealed 4 previously undescribed single nucleotide polymorphisms.
A genomewide homozygosity mapping analysis supported the hypothesis that the gene responsible for a unique vitreoretinal dystrophy is located on chromosome 22q13. No obviously pathogenic mutation was found in the candidate gene, FBLN1.
定位据我们所知尚未被描述的一种常染色体隐性遗传玻璃体视网膜营养不良的致病基因，并分析一个定位于22q13的候选基因（纤连蛋白-1 [FBLN1]）。
使用分布于全基因组的500个微卫星标记（平均间距7.2厘摩 [cM]）进行纯合性定位，并对FBLN1的完整编码区进行突变分析。
在4名患病同胞中，发现所有分析标记在22号染色体上一个区域纯合，该区域从D22S444（着丝粒方向）到D22S1170（端粒方向）跨度为12 cM。优势对数分数在0.017至2.36之间（θ = 0）。对编码相互作用细胞外基质蛋白的FBLN1完整编码区的突变分析，发现了4个先前未被描述的单核苷酸多态性。
全基因组纯合性定位分析支持以下假说，即导致一种独特玻璃体视网膜营养不良的基因位于22号染色体q13区。在候选基因FBLN1中未发现明显的致病突变。
