title: Exome Sequencing Fails to Identify the Genetic Cause of Aicardi Syndrome.
abstract: Aicardi syndrome (AS) is a well-characterized neurodevelopmental disorder with an unknown etiology. In this study, we performed whole-exome sequencing in 11 female patients with the diagnosis of AS, in order to identify the disease-causing gene. In particular, we focused on detecting variants in the X chromosome, including the analysis of variants with a low number of sequencing reads, in case of somatic mosaicism. For 2 of the patients, we also sequenced the exome of the parents to search for de novo mutations. We did not identify any genetic variants likely to be damaging. Only one single missense variant was identified by the de novo analyses of the 2 trios, and this was considered benign. The failure to identify a disease gene in this study may be due to technical limitations of our study design, including the possibility that the genetic aberration leading to AS is situated in a non-exonic region or that the mutation is somatic and not detectable by our approach. Alternatively, it is possible that AS is genetically heterogeneous and that 11 patients are not sufficient to reveal the causative genes. Future studies of AS should consider designs where also non-exonic regions are explored and apply a sequencing depth so that also low-grade somatic mosaicism can be detected.
authors: National Centre for Rare Epilepsy-Related Disorders, Oslo University Hospital, Oslo, Norway.
authors: Caroline
authors: C
authors: Lund
authors: Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Rome, Italy.
authors: Pasquale
authors: P
authors: Striano
authors: Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
authors: Hanne Sørmo
authors: HS
authors: Sorte
authors: NESMOS Department, c/o Sant'Andrea Hospital, Faculty of Medicine and Psychology, University of Rome Sapienza, Rome, Italy.
authors: Pasquale
authors: P
authors: Parisi
authors: Laboratory of Neurogenetics, Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, University of Genoa, 'G. Gaslini' Institute, Genoa, Rome, Italy.
authors: Michele
authors: M
authors: Iacomino
authors: Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
authors: Ying
authors: Y
authors: Sheng
authors: Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
authors: Magnus D
authors: MD
authors: Vigeland
authors: Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
authors: Anne-Marte
authors: AM
authors: Øye
authors: Danish Epilepsy Centre, Dianalund, Odense, Denmark; Institute for Regional Health Services, University of Southern Denmark, Odense, Denmark.
authors: Rikke Steensbjerre
authors: RS
authors: Møller
authors: National Centre for Rare Epilepsy-Related Disorders, Oslo University Hospital, Oslo, Norway; Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
authors: Kaja K
authors: KK
authors: Selmer
authors: Laboratory of Neurogenetics, Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, University of Genoa, 'G. Gaslini' Institute, Genoa, Rome, Italy.
authors: Federico
authors: F
authors: Zara
keywords: Agenesis of corpus callosum; Aicardi syndrome; Whole-exome sequencing; X chromosome