NGS panel analysis in 24 ectopia lentis patients; a clinically relevant test with a high diagnostic yield

被引：18

作者：

Overwater, E. ^{[1
,2
]}

Floor, K. ^{[1
]}

van Beek, D. ^{[1
]}

de Boer, K. ^{[3
]}

van Dijk, T. ^{[1
]}

Hilhorst-Hofstee, Y. ^{[4
]}

Hoogeboom, A. J. M. ^{[5
]}

van Kaam, K. J. ^{[6
]}

van de Kamp, J. M. ^{[1
]}

Kempers, M. ^{[7
]}

Krapels, I. P. C. ^{[6
]}

Kroes, H. Y. ^{[8
]}

Loeys, B. ^{[7
]}

Salemink, S. ^{[7
]}

Stumpel, C. T. R. M. ^{[6
,9
,10
]}

Verhoeven, V. J. M. ^{[5
,11
]}

Wijnands-van den Berg, E. ^{[12
]}

Cobben, J. M. ^{[13
,14
]}

van Tintelen, J. P. ^{[1
,2
]}

Weiss, M. M. ^{[1
]}

Houweling, A. C. ^{[1
]}

Maugeri, A. ^{[1
]}

机构：

[1] Vrije Univ Amsterdam, Med Ctr, Dept Clin Genet, POB 7057, NL-1081 HV Amsterdam, Netherlands

[2] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, Amsterdam, Netherlands

[3] Vrije Univ Amsterdam, Med Ctr, Dept Cardiol, Amsterdam, Netherlands

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

[5] Univ Med Ctr, Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands

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

[7] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Nijmegen, Netherlands

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

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

[10] Maastricht Univ, Sch Oncol & Dev Biol GROW, Maastricht, Netherlands

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

[12] Med Ctr Twente, Dept Pediat, Enschede, Netherlands

[13] St Georges Univ Hosp London, Dept Med Genet, London, England

[14] Univ Amsterdam, Acad Med Ctr, Dept Pediat, Amsterdam, Netherlands

来源：

EUROPEAN JOURNAL OF MEDICAL GENETICS | 2017年 / 60卷 / 09期

关键词：

Ectopia lentis; Next generation sequencing; Gene panel; ADAMTSL4; FBN1; MARFAN-SYNDROME; FOUNDER MUTATION; ADAMTSL4; FIBRILLIN-1; CRANIOSYNOSTOSIS; MICROFIBRILS; PROTEINS; PUPILLAE; FAMILY; GENE;

D O I：

10.1016/j.ejmg.2017.06.005

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Background: Several genetic causes of ectopia lentis (EL), with or without systemic features, are known. The differentiation between syndromic and isolated EL is crucial for further treatment, surveillance and counseling of patients and their relatives. Next generation sequencing (NGS) is a powerful tool enabling the simultaneous, highly-sensitive analysis of multiple target genes. Objective: The aim of this study was to evaluate the diagnostic yield of our NGS panel in EL patients. Furthermore, we provide an overview of currently described mutations in ADAMTSL4, the main gene involved in isolated EL. Methods: A NGS gene panel was analysed in 24 patients with EL. Results: A genetic diagnosis was confirmed in 16 patients (67%). Of these, four (25%) had a heterozygous FBN1 mutation, 12 (75%) were homozygous or compound heterozygous for ADAMTSL4 mutations. The known European ADAMTSL4 founder mutation c.767_786del was most frequently detected. Conclusion: The diagnostic yield of our NGS panel was high. Causative mutations were exclusively identified in ADAMTSL4 and FBN1. With this approach the risk of misdiagnosis or delayed diagnosis can be reduced. The value and clinical implications of establishing a genetic diagnosis in patients with EL is corroborated by the description of two patients with an unexpected underlying genetic condition. (C) 2017 Elsevier Masson SAS. All rights reserved.

引用

页码：465 / 473

页数：9

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