Sohocki M M, Perrault I, Leroy B P, Payne A M, Dharmaraj S, Bhattacharya S S, Kaplan J, Maumenee I H, Koenekoop R, Meire F M, Birch D G, Heckenlively J R, Daiger S P
Human Genetics Center, School of Public Health, Houston, Texas, 77225-0334, USA.
Mol Genet Metab. 2000 Jun;70(2):142-50. doi: 10.1006/mgme.2000.3001.
Leber congenital amaurosis (LCA) is the most severe form of inherited retinal dystrophy and the most frequent cause of inherited blindness in children. LCA is usually inherited in an autosomal recessive fashion, although rare dominant cases have been reported. One form of LCA, LCA4, maps to chromosome 17p13 and is genetically distinct from other forms of LCA. We recently identified the gene associated with LCA4, AIPL1 (aryl-hydrocarbon interacting protein-like 1) and identified three mutations that were the cause of blindness in five families with LCA. In this study, AIPL1 was screened for mutations in 512 unrelated probands with a range of retinal degenerative diseases to determine if AIPL1 mutations cause other forms of inherited retinal degeneration and to determine the relative contribution of AIPL1 mutations to inherited retinal disorders in populations worldwide. We identified 11 LCA families whose retinal disorder is caused by homozygous or compound heterozygous AIPL1 mutations. We also identified affected individuals in two apparently dominant families, diagnosed with juvenile retinitis pigmentosa or dominant cone-rod dystrophy, respectively, who are heterozygous for a 12-bp AIPL1 deletion. Our results suggest that AIPL1 mutations cause approximately 7% of LCA worldwide and may cause dominant retinopathy.
莱伯先天性黑蒙（LCA）是遗传性视网膜营养不良最严重的形式，也是儿童遗传性失明最常见的原因。LCA通常以常染色体隐性方式遗传，不过也有罕见的显性病例报道。LCA的一种形式，即LCA4，定位于17号染色体p13区，在基因上与其他形式的LCA不同。我们最近鉴定出了与LCA4相关的基因AIPL1（芳基烃相互作用蛋白样1），并在五个LCA家系中鉴定出三个导致失明的突变。在本研究中，我们对512名患有一系列视网膜退行性疾病的无关先证者进行了AIPL1突变筛查，以确定AIPL1突变是否会导致其他形式的遗传性视网膜变性，并确定AIPL1突变在全球人群遗传性视网膜疾病中的相对作用。我们鉴定出11个LCA家系，其视网膜疾病由纯合或复合杂合的AIPL1突变引起。我们还在两个明显为显性的家系中鉴定出了受影响个体，分别被诊断为青少年视网膜色素变性或显性视锥 - 视杆营养不良，他们是12个碱基对的AIPL1缺失的杂合子。我们的结果表明，AIPL1突变在全球范围内导致约7%的LCA，并可能导致显性视网膜病变。
