Mis-sense mutation Non-sense mutation Large deletion Consensus splice sites mutation Promoter defects Identification of possible disease causing mutations by systematic genomic sequencing of candidate genes Functional genomics and pre mRNA processing alterations Polymorphisms, atypical and orphan mutations Functional splicing assay Splicing defects Clear possible functional alteration

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Mis-sense mutation Non-sense mutation Large deletion Consensus splice sites mutation Promoter defects Identification of possible disease causing mutations by systematic genomic sequencing of candidate genes Analysis of pre mRNA processing alterations Polymorphisms, atypical and orphan mutations Functional splicing assay (reporter genes) Identification of mutations as possible Splicing defects Clear possible functional alteration Identification of candidate genes by clinical diagnosis RNA expression analysis Verification that mutations act on splicing Identification of trans-acting factors Determination of disease causing mechanism Development of rational therapy approaches, evidence based genetic conseling Clinical evaluation Bioinformatic analysis Experimental validation