Perrault I, Châtelin S, Nancy V, Rozet J M, Gerber S, Ghazi I, Souied E, Dufier J L, Munnich A, de Gunzburg J, Kaplan J
Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U-393, Département de Génétique, Hôpital des Enfants-Malades, Paris, France.
Hum Genet. 1998 Mar;102(3):322-6. doi: 10.1007/s004390050699.
Leber's congenital amaurosis (LCA) is the earliest and most severe of all inherited retinal dystrophies. Recently, we mapped an LCA gene to chromosome 17p13.1 (LCA1) and ascribed the disease to mutations of the retinal guanylate cyclase (ret GC) gene in a subset of families of North African ancestry. Owing to the genetic heterogeneity of LCA and considering that LCA1 results from an impaired production of cGMP in the retina (with permanent closure of cGMP-gated cation channels), we hypothesized that the activation of the cGMP phosphodiesterase (PDE) could trigger the disease by lowering the intracellular cGMP level in the retina. The rod and cone cGMP-PDE inhibitory subunits were regarded therefore as candidate genes in LCA. Here, we report the exclusion of five rod and cone cGMP-PDE subunits in LCA families unlinked to chromosome 17p13.
莱伯先天性黑蒙（LCA）是所有遗传性视网膜营养不良中最早且最严重的一种。最近，我们将一个LCA基因定位到17号染色体p13.1区域（LCA1），并将北非血统的部分家族中的该疾病归因于视网膜鸟苷酸环化酶（ret GC）基因的突变。由于LCA存在遗传异质性，并且考虑到LCA1是由视网膜中cGMP生成受损（cGMP门控阳离子通道永久性关闭）导致的，我们推测cGMP磷酸二酯酶（PDE）的激活可能通过降低视网膜细胞内cGMP水平而引发该疾病。因此，视杆和视锥细胞cGMP - PDE抑制亚基被视为LCA的候选基因。在此，我们报告在与17号染色体p13不连锁的LCA家族中排除了五个视杆和视锥细胞cGMP - PDE亚基。
