Stockton D W, Lewis R A, Abboud E B, Al-Rajhi A, Jabak M, Anderson K L, Lupski J R
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030-3498, USA.
Hum Genet. 1998 Sep;103(3):328-33. doi: 10.1007/s004390050825.
Leber congenital amaurosis (LCA) is a clinically and genetically heterogeneous autosomal recessive retinal dystrophy and the most common genetic cause of congenital visual impairment. We used a DNA pooling strategy comparing the genotypes of affected to unaffected control pools in a genome-wide search for identity-by-descent on a consanguineous Saudi Arabian LCA family. A shift to homozygosity was observed in the affected DNA pool compared with the control pool at linked markers D14S606 and D14S610. Genotyping of individual DNA samples from the entire pedigree for marker D14S74, closely linked to these loci, and several flanking markers confirmed linkage with a ZMAX=13.29 at theta=0.0. These data assign a third locus (LCA3) for LCA to chromosome 14q24. This locus and the previously identified loci are excluded for other Saudi Arabian pedigrees, both confirming that this clinical disorder is genetically heterogeneous and that additional LCA genes remain to be identified.
莱伯先天性黑蒙（LCA）是一种临床和遗传异质性的常染色体隐性视网膜营养不良，也是先天性视力障碍最常见的遗传病因。我们采用DNA池策略，在一个沙特阿拉伯近亲结婚的LCA家系中，通过全基因组搜索同源性，比较患病个体与未患病对照个体的基因型。在连锁标记D14S606和D14S610处，与对照池相比，患病DNA池中观察到纯合性转移。对整个家系中与这些位点紧密连锁的标记D14S74及几个侧翼标记进行个体DNA样本基因分型，证实了在θ=0.0时ZMAX=13.29的连锁关系。这些数据将LCA的第三个基因座（LCA3）定位于14q24染色体。其他沙特阿拉伯家系排除了该基因座和先前确定的基因座，这既证实了这种临床疾病在遗传上是异质性的，也表明仍有待鉴定更多的LCA基因。
