Diagnostic exome sequencing in 266 Dutch patients with visual impairment

被引：106

作者：

Haer-Wigman, Lonneke ^{[1
,2
]}

van Zelst-Stams, Wendy A. G. ^{[1
]}

Pfundt, Rolph ^{[1
,2
]}

van den Born, L. Ingeborgh ^{[3
]}

Klaver, Caroline C. W. ^{[4
,5
]}

Verheij, Joke B. G. M. ^{[6
]}

Hoyng, Carel B. ^{[7
]}

Breuning, Martijn H. ^{[8
]}

Boon, Camiel J. F. ^{[9
]}

Kievit, Anneke J. ^{[10
]}

Verhoeven, Virginie J. M. ^{[4
,10
]}

Pott, Jan W. R. ^{[11
]}

Sallevelt, Suzanne C. E. H. ^{[12
]}

van Hagen, Johanna M. ^{[13
]}

Plomp, Astrid S. ^{[14
]}

Kroes, Hester Y. ^{[15
]}

Lelieveld, Stefan H. ^{[1
,2
]}

Hehir-Kwa, Jayne Y. ^{[1
,2
]}

Castelein, Steven ^{[1
,2
]}

Nelen, Marcel ^{[1
,2
]}

Scheffer, Hans ^{[1
,2
]}

Lugtenberg, Dorien ^{[1
,2
]}

Cremers, Frans P. M. ^{[1
,2
]}

Hoefsloot, Lies ^{[10
]}

Yntema, Helger G. ^{[1
,2
]}

机构：

[1] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, POB 9101, NL-6500 HB Nijmegen, Netherlands

[2] Radboud Inst Mol Life Sci, Nijmegen, Netherlands

[3] Rotterdam Eye Hosp, Rotterdam, Netherlands

[4] Erasmus MC, Dept Ophthalmol, Rotterdam, Netherlands

[5] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands

[6] Univ Groningen, Univ Med Ctr Groningen, Dept Med Genet, Groningen, Netherlands

[7] Radboud Univ Nijmegen, Med Ctr, Dept Ophthalmol, Nijmegen, Netherlands

[8] Leiden Univ, Med Ctr, Dept Clin Genet, Leiden, Netherlands

[9] Leiden Univ, Med Ctr, Dept Ophthalmol, Leiden, Netherlands

[10] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands

[11] Univ Groningen, Univ Med Ctr Groningen, Dept Ophthalmol, Groningen, Netherlands

[12] Maastricht Univ, Med Ctr, Dept Clin Genet, Maastricht, Netherlands

[13] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Amsterdam, Netherlands

[14] Acad Med Ctr, Dept Clin Genet, Amsterdam, Netherlands

[15] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands

来源：

EUROPEAN JOURNAL OF HUMAN GENETICS | 2017年 / 25卷 / 05期

基金：

欧盟地平线“2020”;

关键词：

RETINITIS-PIGMENTOSA; CONGENITAL CATARACT; EYE DISEASE; MUTATIONS; DYSTROPHY; RECOMMENDATIONS; IDENTIFICATION; BLINDNESS; PROTEIN;

D O I：

10.1038/ejhg.2017.9

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Inherited eye disorders have a large clinical and genetic heterogeneity, which makes genetic diagnosis cumbersome. An exome-sequencing approach was developed in which data analysis was divided into two steps: the vision gene panel and exome analysis. In the vision gene panel analysis, variants in genes known to cause inherited eye disorders were assessed for pathogenicity. If no causative variants were detected and when the patient consented, the entire exome data was analyzed. A total of 266 Dutch patients with different types of inherited eye disorders, including inherited retinal dystrophies, cataract, developmental eye disorders and optic atrophy, were investigated. In the vision gene panel analysis (likely), causative variants were detected in 49% and in the exome analysis in an additional 2% of the patients. The highest detection rate of (likely) causative variants was in patients with inherited retinal dystrophies, for instance a yield of 63% in patients with retinitis pigmentosa. In patients with developmental eye defects, cataract and optic atrophy, the detection rate was 50, 33 and 17%, respectively. An exome-sequencing approach enables a genetic diagnosis in patients with different types of inherited eye disorders using one test. The exome approach has the same detection rate as targeted panel sequencing tests, but offers a number of advantages. For instance, the vision gene panel can be frequently and easily updated with additional (novel) eye disorder genes. Determination of the genetic diagnosis improved the clinical diagnosis, regarding the assessment of the inheritance pattern as well as future disease perspective.

引用

页码：591 / 599

页数：9

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