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.

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European Journal of Medical Genetics
Erasmus MC: University Medical Center Rotterdam

Overwater, E., Floor, K. (K.), van Beek, D. M., de Boer, K. (K.), van Dijk, T. (T.), Hilhorst-Hofstee, Y., … Maugeri, A. (2017). NGS panel analysis in 24 ectopia lentis patients; a clinically relevant test with a high diagnostic yield. European Journal of Medical Genetics, 60(9), 465–473. doi:10.1016/j.ejmg.2017.06.005