Development and validation of a comprehensive mutation and deletion detection assay for SDHB, SDHC, and SDHD

BackgroundLack of sequencing validation and complexity of deletion testing hinder genetic diagnosis of SDH-associated paraganglioma/pheochromocytoma.MethodsWe developed sequencing assays and multiplex ligation-dependent probe amplification (MLPA) deletion detection for SDHB, SDHC and SDHD. Clinical performance was validated on 141 blinded samples, previously tested at NIH.ResultsSequencing and deletion detection were highly reproducible and agreed with previous NIH results in 99.3% and 100%, respectively.ConclusionsDNA sequencing combined with MLPA allows reliable and simplified genotyping of SDHB, SDHC and SDHD.