Sensitive quantitative detection of somatic mosaic mutation in 'double cortex' syndrome
| Autor: | Rosemary Burgess, John A. Damiano, Samuel F. Berkovic, Michael S. Hildebrand, Alexander Dobrovic, Renate M Kalnins, Ezgi Ozturk, Hongdo Do, Nigel C. Jones |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
0301 basic medicine Drug Resistant Epilepsy Somatic cell Classical Lissencephalies and Subcortical Band Heterotopias Biology Real-Time Polymerase Chain Reaction 03 medical and health sciences 0302 clinical medicine Germline mutation Intellectual Disability Tissue mosaicism Humans Language Development Disorders Digital polymerase chain reaction Mutation frequency Genetics Mutagenesis General Medicine Phenotype 030104 developmental biology Neurology 1-Alkyl-2-acetylglycerophosphocholine Esterase Mutation Mutation (genetic algorithm) Female Epilepsies Partial Neurology (clinical) Microtubule-Associated Proteins 030217 neurology & neurosurgery |
| Zdroj: | Epileptic Disorders. 19:450-455 |
| ISSN: | 1950-6945 1294-9361 |
| Popis: | 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 individual DNA molecules allowed us to detect the mutation at low level in the brain, despite the low quality of the DNA sample derived from formalin-fixed paraffin-embedded tissue. This low mutation frequency in the brain was consistent with the relatively subtle malformation resolved by magnetic resonance imaging. The presence of the mutation in other tissues from the patient permitted us to predict the timing of mutagenesis. This sensitive methodology will have utility for a variety of other brain malformation syndromes associated with epilepsy for which historical pathological specimens are available and specific somatic mosaic mutations are predicted. |
| Databáze: | OpenAIRE |
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