Sandberg M A, Weigel-DiFranco C, Dryja T P, Berson E L
Berman-Gund Laboratory, Massachusetts Eye and Ear Infirmary, Boston 02114, USA.
Invest Ophthalmol Vis Sci. 1995 Aug;36(9):1934-42.
To determine whether severity of retinitis pigmentosa caused by dominant rhodopsin mutations depends on the location altered by the mutation.
Data from 128 patients (age range, 7 to 73 years), each with 1 to 27 rhodopsin mutations, were analyzed. To approximate normal distributions, visual acuities were converted to ranks and then to the normal form, kinetic visual fields to a V4e test light were converted to equivalent diameters, and dark-adapted sensitivities to an 11 degrees diameter stimulus and electroretinogram (ERG) amplitudes to full-field 0.5-Hz and 30-Hz flashes were converted to common logarithms. Each of these measures was then regressed on age, refractive error (for the ERG), and domain (intradiscal, transmembrane, or cytoplasmic) or codon number of the opsin molecule altered by the mutation.
All five measures of function varied significantly with the domain (P < or = 0.0007) or codon number (P < 0.0001) altered by a mutation; visual acuity, visual field diameter, dark-adapted sensitivity, and ERG amplitudes were highest for mutations altering the intradiscal domain or low-numbered codons and lowest for mutations altering the cytoplasmic domain or high-numbered codons.
These data indicate that severity of disease correlates with the location of the amino acid residue altered by a rhodopsin mutation in dominant retinitis pigmentosa.
确定由显性视紫红质突变引起的视网膜色素变性的严重程度是否取决于突变所改变的位置。
分析了128例患者（年龄范围7至73岁）的数据，每位患者有1至27个视紫红质突变。为了近似正态分布，视力被转换为秩次，然后转换为正态形式，对V4e测试光的动态视野被转换为等效直径，对11度直径刺激的暗适应敏感度以及对全视野0.5赫兹和30赫兹闪光的视网膜电图（ERG）振幅被转换为常用对数。然后将这些测量值中的每一个与年龄、屈光不正（对于ERG）以及突变所改变的视蛋白分子的结构域（盘内、跨膜或胞质）或密码子编号进行回归分析。
所有五项功能测量值均随突变所改变的结构域（P≤0.0007）或密码子编号（P<0.0001）而有显著变化；对于改变盘内结构域或低编号密码子的突变，视力、视野直径、暗适应敏感度和ERG振幅最高，而对于改变胞质结构域或高编号密码子的突变则最低。
这些数据表明，在显性视网膜色素变性中，疾病严重程度与视紫红质突变所改变的氨基酸残基位置相关。
