Rodriguez J A, Herrera C A, Birch D G, Daiger S P
Graduate School of Biomedical Sciences, University of Texas Health Science Center, Houston 77030.
Hum Mutat. 1993;2(3):205-13. doi: 10.1002/humu.1380020309.
To evaluate the extent to which rhodopsin mutations are involved in autosomal dominant forms of retinitis pigmentosa (adRP) we collected DNAs from patients with adRP and screened the rhodopsin coding sequence with single-strand conformational polymorphism (SSCP) analysis and DNA sequencing. This screening revealed a thymidine to guanine transversion at nucleotide 431 (nucleotide sequence numbers as per Genebank) in affected members of one family (RFS04). The nucleotide substitution leads to a missense mutation at the 46th amino acid of rhodopsin. The mutation occurs at an amino acid conserved in mammals and changes the hydrophobic nature of the protein at a transmembrane-spanning region. The mutation causes the substitution of a non-polar hydrophobic amino acid, leucine, for the basic amino acid arginine (Leu46Arg). This nucleotide substitution is unique to the family studied and occurs in the affected individuals in the family. Full-field electroretinograms (ERGs) in four affected members of the family showed nondetectable rod responses at an early age, with markedly reduced cone responses, and a faster than average rate of progression of the phenotype as measured by yearly ERGs.
为了评估视紫红质突变在常染色体显性遗传性视网膜色素变性（adRP）中所起作用的程度，我们收集了adRP患者的DNA，并采用单链构象多态性（SSCP）分析和DNA测序对视紫红质编码序列进行筛查。此次筛查在一个家族（RFS04）的患病成员中发现了第431位核苷酸处的胸腺嘧啶到鸟嘌呤的颠换（核苷酸序列编号参照基因库）。该核苷酸替换导致视紫红质第46位氨基酸处出现错义突变。此突变发生在哺乳动物中保守的一个氨基酸位点，并且改变了蛋白质在跨膜区域的疏水性。该突变导致碱性氨基酸精氨酸被非极性疏水氨基酸亮氨酸替代（Leu46Arg）。这种核苷酸替换是所研究家族特有的，且出现在该家族的患病个体中。该家族4名患病成员的全视野视网膜电图（ERG）显示，在早期未检测到视杆细胞反应，视锥细胞反应明显减弱，并且通过年度ERG测量，该表型的进展速度快于平均水平。
