State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, China.
PLoS One. 2013 Jun 11;8(6):e65546. doi: 10.1371/journal.pone.0065546. Print 2013.
The goal of this study was to identify mutations in 25 known causative genes in 47 unrelated Chinese families with cone-rod dystrophy (CORD).
Forty-seven probands from unrelated families with CORD were recruited. Genomic DNA prepared from leukocytes was analyzed by whole exome sequencing. Variants in the 25 genes were selected and then validated by Sanger sequencing.
Fourteen potential pathogenic mutations, including nine novel and five known, were identified in 10 of the 47 families (21.28%). Homozygous, compound heterozygous, and hemizygous mutations were detected in three, four, or three families, respectively. The 14 mutations in the 10 families were distributed among CNGB3 (three families), PDE6C (two families), ABCA4 (one family), RPGRIP1 (one family), RPGR (two families), and CACNA1F (one family).
This study provides a brief view on mutation spectrum of the 25 genes in a Chinese cohort with CORD. Identification of novel mutations enriched our understanding of variations in these genes and their associated phenotypes. To our knowledge, this is the first systemic exome-sequencing analysis of all of the 25 CORD-associated genes.
本研究旨在鉴定 47 个无血缘关系的 Cone-rod 营养不良（CORD）中国家系中 25 个已知致病基因的突变。
招募了 47 名来自无血缘关系的 CORD 先证者家族的个体。从白细胞中提取基因组 DNA，通过全外显子组测序进行分析。选择 25 个基因中的变异体，然后通过 Sanger 测序进行验证。
在 47 个家系中的 10 个家系（21.28%）中发现了 14 个潜在的致病性突变，包括 9 个新的和 5 个已知的突变。在三个、四个或三个家系中分别检测到纯合子、复合杂合子和半合子突变。这 10 个家系中的 14 个突变分布在 CNGB3（三个家系）、PDE6C（两个家系）、ABCA4（一个家系）、RPGRIP1（一个家系）、RPGR（两个家系）和 CACNA1F（一个家系）中。
本研究提供了中国 CORD 患者 25 个基因的突变谱简要概述。新突变的鉴定丰富了我们对这些基因及其相关表型变异的认识。据我们所知，这是首次对所有 25 个 CORD 相关基因进行系统的外显子组测序分析。
