Camuzat A, Dollfus H, Rozet J M, Gerber S, Bonneau D, Bonnemaison M, Briard M L, Dufier J L, Ghazi I, Leowski C
Service de Génétique, INSERM U. 393, Hôpital des Enfants Malades, Paris, France.
Hum Mol Genet. 1995 Aug;4(8):1447-52. doi: 10.1093/hmg/4.8.1447.
Leber's congenital amaurosis (LCA) is an autosomal recessive disease responsible for congenital blindness. It is the most early and severe form of inherited retinopathy and accounts for 5% of all inherited retinal dystrophies. Here we report the first mapping of a gene for LCA to the distal short arm of chromosome 17 by linkage analysis in 15 multiplex families (Zmax = 5.14 at theta = 0.15 for probe AFM070xg5 at the D17S1353 locus). When our sample was split into two groups according to the ethnic origin of the patients we were able to confirm the presence of a gene for LCA on chromosome 17p by both homozygosity mapping and linkage analysis in five families of Maghrebian origin (LCA1, Zmax = 7.21 at theta = 0.01 at the D17S1353 locus), while negative results were found in 10 families of French ancestry. Haplotype analyses supported the placement of LCA1 between loci D17S796 and D17S786 (maximum likelihood estimate for location of the disease gene over the D17S1353 locus). The genetic heterogeneity of LCA will complicate the prenatal detection of this frequent cause of congenital blindness.
莱伯先天性黑蒙（LCA）是一种常染色体隐性疾病，可导致先天性失明。它是遗传性视网膜病变中最早且最严重的形式，占所有遗传性视网膜营养不良的5%。在此，我们通过对15个多重家庭进行连锁分析，首次将LCA基因定位到17号染色体短臂远端（在D17S1353位点，探针AFM070xg5在θ = 0.15时Zmax = 5.14）。当我们根据患者的种族来源将样本分为两组时，通过纯合性定位和连锁分析，在5个马格里布血统的家庭中证实了17号染色体短臂上存在LCA基因（LCA1，在D17S1353位点，θ = 0.01时Zmax = 7.21），而在10个法国血统的家庭中得到了阴性结果。单倍型分析支持LCA1基因位于D17S796和D17S786位点之间（疾病基因在D17S1353位点的最大似然估计）。LCA的遗传异质性将使这种常见的先天性失明病因的产前检测变得复杂。
