Seyedahmadi Babak Jian, Rivolta Carlo, Keene Julia A, Berson Eliot L, Dryja Thaddeus P
Ocular Molecular Genetics Institute, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA.
Exp Eye Res. 2004 Aug;79(2):167-73. doi: 10.1016/j.exer.2004.03.005.
A screen of the entire coding region of the USH2A gene in 129 unrelated patients with Usher syndrome type II (USH2) and in 146 unrelated patients with non-syndromic autosomal recessive retinitis pigmentosa (ARRP) uncovered 54 different sequence variations, including 18 likely pathogenic mutations (13 frameshift, three nonsense, and two missense), 12 changes of uncertain pathogenicity (11 missense changes and one in-frame deletion), and 24 non-pathogenic rare variants or polymorphisms. Of the 18 likely pathogenic mutations, nine were novel. Among the USH2 patients, 50 (39%) had one or two likely pathogenic mutations. The most common mutant allele in USH2 patients was E767fs, which was found in 29 patients, including one homozygote. Among the ARRP patients, we found 17 (12%) with one or two likely pathogenic mutations. The most common mutant allele in ARRP patients was C759F and it was found in 10 patients. The C759F allele was also found in two USH2 patients; in neither of them was a change in the other allele found. The second most common mutant allele in both patient groups was L1447fs (found in 6/50 USH2 patients and 6/17 ARRP patients). Of the 50+17=67 patients with identified USH2A mutations, only one mutation in one allele was found in 41+12=53 (79%); the reason for the high proportion of patients with only one identified mutation is obscure. Our results indicate that USH2A mutations are found in about 7% of all cases of RP in North America, a frequency similar to the RPGR gene (8%) and the rhodopsin gene (10%).
对129例非综合征性常染色体隐性遗传性色素性视网膜炎（ARRP）患者和146例Ⅱ型Usher综合征（USH2）患者的USH2A基因整个编码区进行筛查，发现了54种不同的序列变异，其中包括18种可能致病的突变（13种移码突变、3种无义突变和2种错义突变）、12种致病性不确定的变化（11种错义变化和1种框内缺失）以及24种非致病性罕见变异或多态性。在这18种可能致病的突变中，有9种是新发现的。在USH2患者中，50例（39%）有1种或2种可能致病的突变。USH2患者中最常见的突变等位基因是E767fs，在29例患者中发现，包括1例纯合子。在ARRP患者中，我们发现17例（12%）有1种或2种可能致病的突变。ARRP患者中最常见的突变等位基因是C759F，在10例患者中发现。在2例USH2患者中也发现了C759F等位基因；在这2例患者中均未发现另一个等位基因有变化。两个患者组中第二常见的突变等位基因是L1447fs（在50例USH2患者中的6例和17例ARRP患者中的6例中发现）。在确定有USH2A突变的50 + 17 = 67例患者中，41 + 12 = 53例（79%）仅在一个等位基因中发现了1种突变；仅发现1种已确定突变的患者比例较高的原因尚不清楚。我们的结果表明，在北美所有RP病例中，约7%存在USH2A突变，这一频率与RPGR基因（8%）和视紫红质基因（10%）相似。
