Department of Laboratory Medicine and Key Laboratory for Human Disease Gene Study of Sichuan Province, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China.
School of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
Clin Chim Acta. 2020 Aug;507:17-22. doi: 10.1016/j.cca.2020.04.006. Epub 2020 Apr 8.
Retinitis pigmentosa (RP) is a group of hereditary retinal diseases that often lead to blindness. Although 80 genes associated with RP have been observed, the genetic mechanism of approximately 40% RP cases remains unknown. This study was to investigate the disease-causing gene in a Han Chinese family with autosomal recessive RP (arRP).
A Chinese arRP family (RP-2373), consisting of three affected siblings and eight unaffected family members, was recruited in this study. All participants underwent complete ophthalmic examinations, including visual field testing, best-corrected visual acuity, fundus photography and electroretinography. Whole exome sequencing was performed on the three patients and Sanger sequencing was utilized to confirm the mutations identified in all family members and 2010 unrelated controls.
A novel homozygous nonsense mutation, c.1231C > T (p.Q411X) in the Cadherin-Related Family Member 1 (CDHR1) gene was identified in the RP-2373 family. The proband and her two affected sisters were found to carry a homozygous mutation that led to a substitution of Glutamine to a stop codon. Other unaffected members and 2010 ethnic-matched controls lacked this mutation. These data showed a complete co-segregation of the CDHR1 mutation with arRP in this family. The p.Q411X mutation was observed to affect highly conserved amino acid residue of CHDR1.
Our study expanded the CDHR1 mutation spectrum of RP in the Chinese population, which might help to better understand RP molecular pathogenesis.
色素性视网膜炎（RP）是一组常导致失明的遗传性视网膜疾病。尽管已经观察到 80 个与 RP 相关的基因，但约 40% RP 病例的遗传机制仍不清楚。本研究旨在探讨一个常染色体隐性遗传 RP（arRP）的汉族家族的致病基因。
本研究纳入了一个由 3 名受累兄弟姐妹和 8 名未受影响的家族成员组成的中国 arRP 家族（RP-2373）。所有参与者均接受了全面的眼科检查，包括视野测试、最佳矫正视力、眼底照相和视网膜电图。对 3 名患者进行了全外显子组测序，对所有家族成员和 2010 名无关对照进行了 Sanger 测序以确认所识别的突变。
在 RP-2373 家族中发现了 Cadherin-Related Family Member 1（CDHR1）基因的一个新的纯合无义突变，c.1231C>T（p.Q411X）。先证者及其 2 名受累姐妹均携带导致谷氨酰胺替换为终止密码子的纯合突变。其他未受影响的成员和 2010 名种族匹配的对照者则缺乏这种突变。这些数据表明，该家族中 CDHR1 突变与 arRP 完全共分离。p.Q411X 突变影响了 CHDR1 高度保守的氨基酸残基。
本研究扩展了中国人群中 RP 的 CDHR1 突变谱，这可能有助于更好地理解 RP 的分子发病机制。
