Abstract:
Cyclic nucleotide-gated channel β1 (CNGB1) encodes the 240-kDa β subunit of the rod photoreceptor cyclic nucleotide-gated ion channel. Disease-causing sequence variants in CNGB1 lead to autosomal recessive rod-cone dystrophy/retinitis pigmentosa (RP). We herein present a comprehensive review and analysis of all previously reported CNGB1 sequence variants, and add 22 novel variants, thereby enlarging the spectrum to 84 variants in total, including 24 missense variants (two of which may also affect splicing), 21 nonsense, 19 splicing defects (7 at noncanonical positions), 10 small deletions, 1 small insertion, 1 small insertion-deletion, 7 small duplications, and 1 gross deletion. According to the American College of Medical Genetics and Genomics classification criteria, 59 variants were considered pathogenic or likely pathogenic and 25 were variants of uncertain significance. In addition, we provide further phenotypic data from 34 CNGB1-related RP cases, which, overall, are in line with previous findings suggesting that this form of RP has long-term retention of useful central vision despite the early onset of night blindness, which is valuable for patient counseling, but also has implications for it being considered a priority target for gene therapy trials.
摘要:
环核苷酸门控通道β1(CNGB1)编码视杆光感受器环核苷酸门控通道的240kDaβ亚基。CNGB1中的致病序列变异导致常染色体隐性视锥营养不良/色素性视网膜炎(RP)。我们在此对所有以前报道的CNGB1序列变体进行了全面的回顾和分析,并添加22种新颖的变体,从而将光谱扩大到总共84个变体,包括24个错义变体(其中两个也可能影响剪接),21废话,19个拼接缺陷(7个在非规范位置),10个小删除,1个小插入,1个小的插入-删除,7个小重复,和1个总删除。根据美国医学遗传学和基因组学学院的分类标准,59个变体被认为是致病性或可能致病性的,25个变体具有不确定的意义。此外,我们提供了34例CNGB1相关RP病例的进一步表型数据,which,总的来说,与先前的发现一致,表明尽管夜盲症的早期发作,这种形式的RP仍可长期保留有用的中枢视力,这对病人咨询很有价值,但它也被认为是基因治疗试验的优先靶点。