Ignazio S Piras1,2, Gabrielle Mills1,2, Lorida Llaci1,2, Marcus Naymik1,2, Keri Ramsey1,2, Newell Belnap1,2, Chris D Balak1,2, Wayne M Jepsen1,2, Szabolcs Szelinger1,2,3, Ashley L Siniard1,2, Candace R Lewis1,2, Madison LaFleur1,2, Ryan F Richholt1,2, Matt D De Both1,2, Kristiina Avela4, Sampathkumar Rangasamy1,2, David W Craig1,2,5, Vinodh Narayanan1,2, Irma Järvelä6, Matthew J Huentelman1,2, Isabelle Schrauwen1,2,7. 1. Center for Rare Childhood Disorders, Translational Genomics Research Institute, 445 N 5th Street, Phoenix, AZ, USA. 2. Neurogenomics Division, Translational Genomics Research Institute, 445 N 5th Street, Phoenix, AZ, USA. 3. Department of Pathology & Laboratory Medicine, David Geffen School of Medicine, University of California, 10833 Le Conte Ave, Los Angeles, CA 90095, USA. 4. Department of Clinical Genetics, Helsinki University Hospital, Meilahdentie 2, FI-00029 Helsinki, Finland. 5. University of Southern California, Keck School of Medicine, Department of Translational Genomics, Los Angeles, NRT 1450 Biggy Street, CA 90033, USA. 6. Department of Medical Genetics, University of Helsinki, Haartmaninkatu 8, 00251 Helsinki, Finland. 7. Center for Statistical Genetics, Department of Molecular & Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Abstract
AIM: To explore differential DNA methylation (DNAm) in Aicardi syndrome (AIC), a severe neurodevelopmental disorder with largely unknown etiology. PATIENTS & METHODS: We characterized DNAm in AIC female patients and parents using the Illumina 450 K array. Differential DNAm was assessed using the local outlier factor algorithm, and results were validated via qPCR in a larger set of AIC female patients, parents and unrelated young female controls. Functional epigenetic modules analysis was used to detect pathways integrating both genome-wide DNAm and RNA-seq data. RESULTS & CONCLUSION: We detected differential methylation patterns in AIC patients in several neurodevelopmental and/or neuroimmunological networks. These networks may be part of the underlying pathogenic mechanisms involved in the disease.
AIM: To explore differential DNA methylation (DNAm) in Aicardi syndrome (AIC), a severe neurodevelopmental disorder with largely unknown etiology. PATIENTS & METHODS: We characterized DNAm in AIC female patients and parents using the Illumina 450 K array. Differential DNAm was assessed using the local outlier factor algorithm, and results were validated via qPCR in a larger set of AIC female patients, parents and unrelated young female controls. Functional epigenetic modules analysis was used to detect pathways integrating both genome-wide DNAm and RNA-seq data. RESULTS & CONCLUSION: We detected differential methylation patterns in AICpatients in several neurodevelopmental and/or neuroimmunological networks. These networks may be part of the underlying pathogenic mechanisms involved in the disease.
Entities:
Keywords:
Aicardi syndrome; DNA methylation; KCNAB3