Item

Abstract

Next-generation sequencing (NGS) techniques have greatly accelerated the molecular elucidation of Mendelian disorders, and affordable NGS-based diagnostic tests are around the corner that promise to detect or rule out mutations in specific subsets of the known disease genes. Whole exome sequencing and shortly afterwards whole genome sequencing (WGS) will become an even more comprehensive alternative to such targeted tests. In view of the current enthusiasm to implement these methods, but also given their rapidly dropping costs, it is quite possible that WGS will soon be adopted as universal intake test in Clinical Genetics. Central databases and large-scale genotype-phenotype comparisons will be required to progressively identify the clinically relevant sequence variants and to distinguish them from neutral polymorphisms in the human genome, and these databases will become indispensable for the interpretation of individual genome sequences. In this scenario, there will be massively growing demand for genetic counselling, but the need for experienced syndromologists will not increase proportionally, as the success of the diagnostic process will become far less dependent on the ability of clinical geneticists to reliably recognize genetic syndromes.