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A de novo truncating mutation in ASXL1 associated with segmental overgrowth

Efthymiou, S; Salpietro, V; Pironti, E; Bonsignore, M; Ferrazzoli, V; Di Rosa, G; Houlden, H; (2019) A de novo truncating mutation in ASXL1 associated with segmental overgrowth. Journal of Genetics , 98 (5) , Article 108. 10.1007/s12041-019-1155-5. Green open access

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Abstract

Mutations 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 rarest genetic 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.

Type: Article
Title: A de novo truncating mutation in ASXL1 associated with segmental overgrowth
Open access status: An open access version is available from UCL Discovery
DOI: 10.1007/s12041-019-1155-5
Publisher version: https://doi.org/10.1007/s12041-019-1155-5
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
Keywords: Bohring-Opitz syndrome, ASXL1 gene, segmental overgrowth, nevus flammeus, macrocephaly capillary malformation
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10094644
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