Clinical exome sequencing for inherited retinal degenerations at a tertiary care center.
Clinical exome sequencing for inherited retinal degenerations at a tertiary care center.
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DOI：
10.1038/s41598-022-13026-2
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发表时间：
2022-06-07
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
遗传性视网膜变性是一种以进行性视力下降为特征的临床和遗传异质性疾病。这项研究旨在评估外显子组测序(ES)对一组未选定的遗传性视网膜疾病患者的诊断效率。这是一项对357名无关患者的回顾性研究，这些患者被诊断为视网膜疾病，他们接受了临床ES。根据ACMG的建议对ES的变体进行筛选、优先排序和分类。临床诊断包括视锥细胞营养不良(60%)、黄斑营养不良(20%)、视锥细胞营养不良(9%)、视锥细胞营养不良(4%)和其他表型(7%)。大多数(74%)是单身人士，6%是三胞胎。24%的病例得到了确认的分子诊断。在6%的病例中，两个致病变异体被鉴定为阶段未知，使潜在的分子诊断率达到 ~ 30%。包括不确定意义的变异(VUS)在内，57%的病例报告了潜在的重大发现。在分子诊断确诊的病例中，在不止一个患者身上发现了EYS、ABCA4、USH2A、KIZ、CERKL、DHDDS、PROM1、NR2E3、CNGB1、ABCC6、PRPH2、Rho、PRPF31、PRPF8、SNRNP200、RP1、CHM和RPGR的变异。我们的结果支持临床胚胎干细胞在诊断遗传性异质性视网膜疾病中的应用。
Inherited retinal degenerations are clinically and genetically heterogeneous diseases characterized by progressive deterioration of vision. This study aimed at assessing the diagnostic yield of exome sequencing (ES) for an unselected cohort of individuals with hereditary retinal disorders. It is a retrospective study of 357 unrelated affected individuals, diagnosed with retinal disorders who underwent clinical ES. Variants from ES were filtered, prioritized, and classified using the ACMG recommendations. Clinical diagnosis of the individuals included rod-cone dystrophy (60%), macular dystrophy (20%), cone-rod dystrophy (9%), cone dystrophy (4%) and other phenotypes (7%). Majority of the cases (74%) were singletons and 6% were trios. A confirmed molecular diagnosis was obtained in 24% of cases. In 6% of cases, two pathogenic variants were identified with phase unknown, bringing the potential molecular diagnostic rate to ~ 30%. Including the variants of uncertain significance (VUS), potentially significant findings were reported in 57% of cases. Among cases with a confirmed molecular diagnosis, variants in EYS, ABCA4, USH2A, KIZ, CERKL, DHDDS, PROM1, NR2E3, CNGB1, ABCC6, PRPH2, RHO, PRPF31, PRPF8, SNRNP200, RP1, CHM, RPGR were identified in more than one affected individual. Our results support the utility of clinical ES in the diagnosis of genetically heterogeneous retinal disorders.
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影响因子：
5.6
作者：
Dockery A;Whelan L;Humphries P;Farrar GJ
通讯作者：
Farrar GJ
DOI：
10.1038/gim.2013.73
发表时间：
2013-07
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
--
作者：
通讯作者：
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下一代测序揭示了一大群遗传性视网膜营养不良患者的基因型-表型相关性和突变谱
影响因子：
8.8
作者：
Huang, Xiu-Feng;Huang, Fang;Jin, Zi-Bing
通讯作者：
Jin, Zi-Bing
影响因子：
4.6
作者：
Carrigan M;Duignan E;Malone CP;Stephenson K;Saad T;McDermott C;Green A;Keegan D;Humphries P;Kenna PF;Farrar GJ
通讯作者：
Farrar GJ
对1000个遗传性视网膜疾病的连续家庭进行临床焦点分子研究。
影响因子：
13.7
作者：
Stone EM;Andorf JL;Whitmore SS;DeLuca AP;Giacalone JC;Streb LM;Braun TA;Mullins RF;Scheetz TE;Sheffield VC;Tucker BA
通讯作者：
Tucker BA