Saumya S Jamuar, Anh-Thu N Lam, Martin Kircher, Alissa M D'Gama, Jian Wang, Brenda J Barry, Xiaochang Zhang, Robert Sean Hill, Jennifer N Partlow, Aldo Rozzo, Sarah Servattalab, Bhaven K Mehta, Meral Topcu, Dina Amrom, Eva Andermann, Bernard Dan, Elena Parrini, Renzo Guerrini, Ingrid E Scheffer, Samuel F Berkovic, Richard J Leventer, Yiping Shen, Bai Lin Wu, A James Barkovich, Mustafa Sahin, Bernard S Chang, Michael Bamshad, Deborah A Nickerson, Jay Shendure, Annapurna Poduri, Timothy W Yu, Christopher A Walsh
BACKGROUND: Although there is increasing recognition of the role of somatic mutations in genetic disorders, the prevalence of somatic mutations in neurodevelopmental disease and the optimal techniques to detect somatic mosaicism have not been systematically evaluated. METHODS: Using a customized panel of known and candidate genes associated with brain malformations, we applied targeted high-coverage sequencing (depth, ≥200×) to leukocyte-derived DNA samples from 158 persons with brain malformations, including the double-cortex syndrome (subcortical band heterotopia, 30 persons), polymicrogyria with megalencephaly (20), periventricular nodular heterotopia (61), and pachygyria (47)...
August 21, 2014: New England Journal of Medicine