Efthymiou, StephanieSalpietro, VincenzoPironti, EricaBonsignore, MariaFerrazzoli, ValentinaRosa, Gabriella DiHoulden, Henry2020-11-182020-11-182019-11Efthymiou Stephanie, Salpietro Vincenzo, Pironti Erica, Bonsignore Maria, Ferrazzoli Valentina, Rosa Gabriella Di, Houlden Henry. A de novo truncating mutation in ASXL1 associated with segmental overgrowth. Journal of Genetics. 2019 Nov; 98: 1-50022-13330973-7731http://imsear.searo.who.int/handle/123456789/215451Mutations in genes involved in chromatin remodelling have been implicated in broad phenotypes of congenital abnormalities and neurodevelopment. However, limited genotype–phenotype correlations are available for some of the rarestgenetic disorders that affect chromatin regulation. We hereby describe a 12-year-old girl presented at birth with severe hypotonia, developmental delay, a mid-line capillary malformation and distinctive craniofacial features. During the natural history of her disease, the girl developed severe spasticity and drug-resistant seizures, leading to a diagnosis of Bohring–Opitz syndrome (BOS). We performed whole-exome sequencing (WES) and identified a de novo mutation in ASXL1 (c.2033dupG) which results in the introduction of a premature stop codon (p.R678fs*6). ASXL1 encodes a polycomb repressive complex protein implicated in chromatin regulation and de novo mutations are a known cause of BOS. Phenotypes with segmental craniofacial overgrowth associated to midline capillary malformations enlarge the clinical spectrum of BOS at onset and further expand the differential diagnosis in ASXL1 mutation carriers.Bohring–Opitz syndromeASXL1 genesegmental overgrowthnevus flammeusmacrocephaly capillary malformation.Journal ArticleIndiaDepartment of Neuromuscular Disorders, Institute of Neurology, University College London, London WC1N 3BG, UKDepartment of Human Pathology of the Adult and Developmental Age ‘Gaetano Barresi’, Unit of Child Neurology and Psychiatry, University of Messina, 98125 Messina, ItalyDepartment of Biomedicine and Prevention, University of Tor Vergata, 00133 Rome, Italy