Journal article

Sensitive quantitative detection of somatic mosaic mutation in "double cortex" syndrome

John A Damiano, Hongdo Do, Ezgi Ozturk, Rosemary Burgess, Renate Kalnins, Nigel C Jones, Alexander Dobrovic, Samuel F Berkovic, Michael S Hildebrand



Somatic mutation of the lissencephaly-1 gene is a cause of subcortical band heterotopia ("double cortex"). The severity of the phenotype depends on the level of mutation in brain tissue. Detecting and quantifying low-level somatic mosaic mutations is challenging. Here, we utilized droplet digital PCR, a sensitive method to detect low-level mutation. Droplet digital PCR was used in concert with classic genotyping techniques (SNaPshot assays and pyrosequencing) to detect and characterize the tissue mosaicism of a somatic mutation (LIS1 c.190A>T; p.K64X) in a patient with posterior bilateral SBH and refractory epilepsy. The high sensitivity of droplet digital PCR and the ability to target indiv..

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Awarded by National Health and Medical Research Council Program

Awarded by RD Wright Career Development Fellowship

Funding Acknowledgements

We thank the patient for her participation in this study. Rebekah Stubbs (Epilepsy Research Centre, University of Melbourne) is acknowledged for performing genomic DNA extractions. This study was supported by National Health and Medical Research Council Program Grant 1091593 to SFB, Project Grant 1129054 to SFB, Project Grant 1079058 to MSH, and a RD Wright Career Development Fellowship (1063799) to MSH.SFB discloses payments from UCB Pharma, Novartis Pharmaceuticals, Sanofi-Aventis, and Jansen Cilag for lectures and educational presentations, and a patent for SCN1A testing held by Bionomics Inc and licensed to various diagnostic companies. AD has given lectures and educational presentations for Bio-Rad. The remaining authors have no conflicts of interest to declare.