[Methods for the analysis of large gene deletions and their application in some hereditary diseases]

Complete or partial gene deletions and copy number variations of disease-causing genes have pathophysiological significance in several monogenic hereditary diseases. Direct DNA sequencing is not suitable for the detection of these genetic abnormalities. In this work, authors review methods of large gene deletion testing and present their own results in two monogenic diseases to demonstrate the application of current methods in clinical practice. Classical methods (chromosome banding, Southern-hybridisation, fluorescent in situ hybridisation), polymerase chain reaction-based techniques (denaturing high performance liquid chromatography, quantitative real-time polymerase chain reaction, microsatellite marker analysis, multiple amplifiable probe hybridisation, multiple ligation probe amplification) as well as techniques based on recent advances in bioinformatics (comparative genome hybridisation, array-based analysis) are presented. Finally, authors present their own findings on large deletion testing of the VHL gene using quantitative real-time polymerase chain reaction and multiple ligation probe amplification in patients with von Hippel-Lindau disease and review a simple polymerase chain reaction method for the detection of large deletion of the CYP21A2 gene in patients with congenital adrenal hyperplasia.