Overwater E, Floor K, van Beek D, de Boer K, van Dijk T, Hilhorst-Hofstee Y, Hoogeboom A J M, van Kaam K J, van de Kamp J M, Kempers M, Krapels I P C, Kroes H Y, Loeys B, Salemink S, Stumpel C T R M, Verhoeven V J M, Wijnands-van den Berg E, Cobben J M, van Tintelen J P, Weiss M M, Houweling A C, Maugeri A
Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands; Department of Clinical Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.
Eur J Med Genet. 2017 Sep;60(9):465-473. doi: 10.1016/j.ejmg.2017.06.005. Epub 2017 Jun 19.
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.
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.
A NGS gene panel was analysed in 24 patients with EL.
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.
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.
已知有几种导致晶状体异位（EL）的遗传原因，有或无全身特征。综合征性EL和孤立性EL的鉴别对于患者及其亲属的进一步治疗、监测和咨询至关重要。下一代测序（NGS）是一种强大的工具，能够同时对多个靶基因进行高灵敏度分析。
本研究的目的是评估我们的NGS检测板对EL患者的诊断率。此外，我们概述了目前已描述的与孤立性EL相关的主要基因ADAMTSL4中的突变。
对24例EL患者进行了NGS基因检测板分析。
16例患者（67%）确诊有基因诊断结果。其中，4例（25%）有杂合性FBN1突变，12例（75%）为ADAMTSL4突变的纯合子或复合杂合子。最常检测到已知的欧洲ADAMTSL4始祖突变c.767_786del。
我们的NGS检测板诊断率很高。仅在ADAMTSL4和FBN1中鉴定出致病突变。通过这种方法可以降低误诊或延迟诊断的风险。两名患有意外潜在遗传疾病患者的描述证实了对EL患者进行基因诊断的价值和临床意义。
