A de novo truncating mutation in ASXL1 associated with segmental overgrowth

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dc.contributor.authorEfthymiou, Stephanieen_US
dc.contributor.authorSalpietro, Vincenzoen_US
dc.contributor.authorPironti, Ericaen_US
dc.contributor.authorBonsignore, Mariaen_US
dc.contributor.authorFerrazzoli, Valentinaen_US
dc.contributor.authorRosa, Gabriella Dien_US
dc.contributor.authorHoulden, Henryen_US
dc.date.accessioned2020-11-18T10:20:50Z
dc.date.available2020-11-18T10:20:50Z
dc.date.issued2019-11
dc.description.abstractMutations 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.en_US
dc.identifier.affiliationsDepartment of Neuromuscular Disorders, Institute of Neurology, University College London, London WC1N 3BG, UKen_US
dc.identifier.affiliationsDepartment of Human Pathology of the Adult and Developmental Age ‘Gaetano Barresi’, Unit of Child Neurology and Psychiatry, University of Messina, 98125 Messina, Italyen_US
dc.identifier.affiliationsDepartment of Biomedicine and Prevention, University of Tor Vergata, 00133 Rome, Italyen_US
dc.identifier.citationEfthymiou 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: 1-5en_US
dc.identifier.issn0022-1333
dc.identifier.issn0973-7731
dc.identifier.placeIndiaen_US
dc.identifier.urihttps://imsear.searo.who.int/handle/123456789/215451
dc.languageenen_US
dc.publisherIndian Academy of Sciencesen_US
dc.relation.volume98en_US
dc.source.urihttps://doi.org/10.1007/s12041-019-1155-5en_US
dc.subjectBohring–Opitz syndromeen_US
dc.subjectASXL1 geneen_US
dc.subjectsegmental overgrowthen_US
dc.subjectnevus flammeusen_US
dc.subjectmacrocephaly capillary malformation.en_US
dc.titleA de novo truncating mutation in ASXL1 associated with segmental overgrowthen_US
dc.typeJournal Articleen_US
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