Journal of Genetics

, 98:108 | Cite as

A de novo truncating mutation in ASXL1 associated with segmental overgrowth

  • Stephanie Efthymiou
  • Vincenzo Salpietro
  • Erica Pironti
  • Maria Bonsignore
  • Valentina Ferrazzoli
  • Gabriella Di Rosa
  • Henry HouldenEmail author
Research Note


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.


Bohring–Opitz syndrome ASXL1 gene segmental overgrowth nevus flammeus macrocephaly capillary malformation. 



We gratefully acknowledge the family for the enthusiastic collaboration to this study. This study was supported in part by The Wellcome Trust in equipment and strategic award (Synaptopathies) funding (WT093205 MA and WT104033AIA).


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Copyright information

© Indian Academy of Sciences 2019

Authors and Affiliations

  1. 1.Department of Neuromuscular Disorders, Institute of NeurologyUniversity College LondonLondonUK
  2. 2.Department of Human Pathology of the Adult and Developmental Age ‘Gaetano Barresi’, Unit of Child Neurology and PsychiatryUniversity of MessinaMessinaItaly
  3. 3.Department of Biomedicine and PreventionUniversity of Tor VergataRomeItaly

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