Rivolta C, Peck N E, Fulton A B, Fishman G A, Berson E L, Dryja T P
Ocular Molecular Genetics Institute, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA.
Hum Mutat. 2001 Dec;18(6):550-1. doi: 10.1002/humu.1243.
Mutations in CRX, a photoreceptor-specific transcription factor, can cause Leber congenital amaurosis (LCA), cone-rod dystrophy (CORD), and retinitis pigmentosa (RP), all of which feature severe visual impairment. Upon screening 55 patients with Leber congenital amaurosis, 75 patients with cone-rod dystrophy, 13 with cone dystrophy, and 36 with recessive or isolate RP for changes in the CRX sequence, we found two patients with Leber congenital amaurosis who carried heterozygously one of two novel frameshift mutations. The first mutation, Tyr191(1-bp del), was a de novo change and the second change, Pro263(1-bp del) was inherited from the proband's affected father. Both mutations are predicted to encode mutant versions of CRX with altered carboxy termini. We also found a previously reported missense mutation, Arg41Gln, heterozygously in a 47-year-old patient with a form of RP. The missense change Val242Met was found in an isolate case of CORD and no controls; however, its pathogenicity remains uncertain because only limited segregation analysis was possible. A nonpathogenic missense change, Ala158Thr, was found to be a variant present at relatively high frequency among African-Americans.
视锥细胞特异性转录因子CRX的突变可导致莱伯先天性黑矇（LCA）、视锥-视杆营养不良（CORD）和色素性视网膜炎（RP），所有这些疾病都有严重的视力损害。在对55例莱伯先天性黑矇患者、75例视锥-视杆营养不良患者、13例视锥营养不良患者和36例隐性或孤立性RP患者进行CRX序列变化筛查时，我们发现两名莱伯先天性黑矇患者携带了两种新型移码突变中的一种杂合子。第一种突变Tyr191(1-bp del)是一种新发突变，第二种突变Pro263(1-bp del)是从先证者患病的父亲那里遗传而来。预计这两种突变都会编码羧基末端改变的CRX突变体。我们还在一名47岁的某种形式RP患者中杂合地发现了一个先前报道的错义突变Arg41Gln。错义改变Val242Met在一例孤立的CORD病例中被发现，且未在对照中发现；然而，由于只能进行有限的分离分析，其致病性仍不确定。一种无致病性的错义改变Ala158Thr被发现是非洲裔美国人中相对高频出现的一种变体。
