title: Aortic Dilatation Associated With a De Novo Mutation in the SOX18 Gene: Expanding the Clinical Spectrum of Hypotrichosis-Lymphedema-Telangiectasia Syndrome.
abstract: BACKGROUND
  We report a 13-year-old female patient followed since birth for multiple rare congenital defects, including hypotrichosis, telangiectasia, and severe dilatation of the ascending aorta.
  
  
  METHODS
  Comprehensive phenotype assessment throughout childhood included repeated echocardiographic measurements, evaluation of renal function, and immunohistochemical analysis of skin biopsy samples. Whole-exome sequencing was performed for the patient and both unaffected parents.
  
  
  RESULTS
  We identified a novel de novo mutation in the transcription factor SOX18 (c.481C>T:p.Gln161*) in the patient, which was absent in all unaffected family members. Echocardiography revealed early onset and progressive dilatation of the ascending aorta. Skin biopsy results confirmed the defects of the blood vasculature in the presence of intact lymphatic vessels. Assessment of renal function did not show any signs of renal problems or renal failure in the patient.
  
  
  CONCLUSIONS
  The genetic finding of a pathogenic SOX18 mutation enabled the diagnosis of the rare hypotrichosis-lymphedema-telangiectasia syndrome in our patient. The identification of a novel stop gain mutation in the SOX18 gene in association with dilatation of the aorta highlights the importance of this gene during the development of the circulatory system. Our study highlights the importance of whole-exome sequencing in the rapid identification of genes and gene mutations involved in rare conditions and thus expanding the knowledge and spectrum of clinical manifestations associated with them.
authors.affiliation: Cardiovascular Genetics, Department of Pediatrics, CHU Sainte-Justine, Université de Montréal, Montréal, Québec, Canada; Faculty of Biology, University of Muenster, Muenster, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Wünnemann
authors.affiliation: Department of Pathology, CHU Sainte-Justine, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Victor
authors.initials: V
authors.lastname: Kokta
authors.affiliation: Cardiovascular Genetics, Department of Pediatrics, CHU Sainte-Justine, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Séverine
authors.initials: S
authors.lastname: Leclerc
authors.affiliation: Cardiovascular Genetics, Department of Pediatrics, CHU Sainte-Justine, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Maryse
authors.initials: M
authors.lastname: Thibeault
authors.affiliation: Dermatology Service, Department of Pediatrics, CHU Sainte-Justine, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Catherine
authors.initials: C
authors.lastname: McCuaig
authors.affiliation: Dermatology Service, Department of Pediatrics, CHU Sainte-Justine, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Afshin
authors.initials: A
authors.lastname: Hatami
authors.affiliation: Centre de Recherche, Department of Pediatrics, CHU Sainte-Justine, Université de Montreal, Montréal, Québec, Canada.
authors.forename: Chantal
authors.initials: C
authors.lastname: Stheneur
authors.affiliation: Centre de Recherche, Department of Pediatrics, CHU Sainte-Justine, Université de Montreal, Montréal, Québec, Canada.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Grenier
authors.affiliation: Centre de Recherche, Department of Pediatrics, CHU Sainte-Justine, Université de Montreal, Montréal, Québec, Canada; Ontario Instiute for Cancer Research, MaRS Centre, Toronto, Ontario, Canada.
authors.forename: Philip
authors.initials: P
authors.lastname: Awadalla
authors.affiliation: Centre de Recherche, Department of Pediatrics, CHU Sainte-Justine, Université de Montreal, Montréal, Québec, Canada.
authors.forename: Grant A
authors.initials: GA
authors.lastname: Mitchell
authors.affiliation: Cardiovascular Genetics, Department of Pediatrics, CHU Sainte-Justine, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Gregor
authors.initials: G
authors.lastname: Andelfinger
authors.affiliation: Cardiovascular Genetics, Department of Pediatrics, CHU Sainte-Justine, Université de Montréal, Montréal, Québec, Canada. Electronic address: ch.preuss@gmail.com.
authors.forename: Christoph
authors.initials: C
authors.lastname: Preuss
mesh_terms: D000293:Adolescent; D017545:Aortic Aneurysm, Thoracic / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D001706:Biopsy; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D004452:Echocardiography; D005260:Female; D006801:Humans; D007039:Hypotrichosis / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D008209:Lymphedema / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D055760:SOXF Transcription Factors / Q000235:genetics* / Q000378:metabolism; D013684:Telangiectasis / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism
chemical_list: C095473:SOX18 protein, human; D055760:SOXF Transcription Factors; D004247:DNA