Determinants of diagnostic yield in a multi-ethnic Asian inherited retinal disease cohort.

IF 3.7 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Jane Andrea Lieviant, Choi Mun Chan, Yasmin Bylstra, Kanika Jain, Jing Xian Teo, Wan Wan Lim, Sylvia Kam, Tang Wei Chao, Nellie Chai Bin Siew, Sonia Davila, Eranga Nishanthie Vithana, Ranjana Sanjay Mathur, Tien-En Tan, Patrick Tan, Saumya S Jamuar, Beau James Fenner, Weng Khong Lim
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引用次数: 0

Abstract

As the discovery of new genes causing inherited retinal disease (IRD) has plateaued, we look to other factors which could be used to maximize diagnostic yield. We analyzed whole-exome sequencing (WES) data from 506 IRD probands, focusing on the interplay between diagnostic yield, age of symptom onset or diagnosis, family history, and initial clinical diagnosis. The cohort's overall diagnostic yield was 49.2%. Diagnostic yield was negatively correlated with the age of symptom onset and positively correlated with the number of affected family members. Diseases with distinctive clinical presentations such as Bietti crystalline dystrophy (BCD) or Leber congenital amaurosis (LCA) were more reliably diagnosed than more common and heterogeneous diseases like retinitis pigmentosa (RP) and cone-rod dystrophy (CRD). Recurrent genes and variants in this Chinese-majority cohort resemble those found in Chinese cohort studies but differ from populations of European descent, with implications for the design and prioritization of gene therapies. These insights may help optimize the diagnostic utility of genetic testing for IRDs, enhance the delivery of genetic counseling for patients, and guide the development of more inclusive targeted therapies.

亚洲多种族遗传性视网膜疾病队列诊断率的决定因素
由于发现导致遗传性视网膜疾病(IRD)的新基因已经趋于稳定,我们寻找其他可用于最大限度地提高诊断率的因素。我们分析了506个IRD先证者的全外显子组测序(WES)数据,重点研究了诊断率、症状发病或诊断年龄、家族史和初始临床诊断之间的相互作用。该队列的总诊断率为49.2%。诊断率与发病年龄呈负相关,与患病家庭成员数呈正相关。具有特殊临床表现的疾病,如Bietti结晶性营养不良(BCD)或Leber先天性黑朦(LCA)的诊断比更常见和异质性的疾病,如视网膜色素变性(RP)和锥杆营养不良(CRD)更可靠。在这个华人占多数的队列中,复发性基因和变异与华人队列研究中发现的相似,但与欧洲血统人群不同,这对基因治疗的设计和优先级有影响。这些见解可能有助于优化基因检测对ird的诊断效用,加强对患者的遗传咨询,并指导更具包容性的靶向治疗的发展。
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来源期刊
European Journal of Human Genetics
European Journal of Human Genetics 生物-生化与分子生物学
CiteScore
9.90
自引率
5.80%
发文量
216
审稿时长
2 months
期刊介绍: The European Journal of Human Genetics is the official journal of the European Society of Human Genetics, publishing high-quality, original research papers, short reports and reviews in the rapidly expanding field of human genetics and genomics. It covers molecular, clinical and cytogenetics, interfacing between advanced biomedical research and the clinician, and bridging the great diversity of facilities, resources and viewpoints in the genetics community. Key areas include: -Monogenic and multifactorial disorders -Development and malformation -Hereditary cancer -Medical Genomics -Gene mapping and functional studies -Genotype-phenotype correlations -Genetic variation and genome diversity -Statistical and computational genetics -Bioinformatics -Advances in diagnostics -Therapy and prevention -Animal models -Genetic services -Community genetics
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