title: GATA2 null mutation associated with incomplete penetrance in a family with Emberger syndrome.
abstract: BACKGROUND
  GATA2 mutations are associated with several conditions, including Emberger syndrome which is the association of primary lymphedema with hematological anomalies and an increased risk for myelodysplasia and leukemia.
  
  
  OBJECTIVE
  To describe a family with Emberger syndrome with incomplete penetrance.
  
  
  METHODS
  A DNA sequencing of GATA2 gene was performed in the parents and offspring (five individuals in total).
  
  
  RESULTS
  The family consisted of 5 individuals with a GATA2 null mutation (c.130G>T, p.Glu44*); three of them were affected (two of which were deceased) while two remained unaffected at the age of 40 and 13 years old. The three affected siblings (two boys and one girl) presented with lymphedema of the lower limbs, recurrent warts, epistaxis and recurrent infections. Two died due to hematological abnormalities (AML and pancytopenia). In contrast, the two other family members who carry the same mutation (the mother and one brother) have not presented any symptoms and their blood tests remain normal.
  
  
  CONCLUSIONS
  Incomplete penetrance may indicate that GATA2 haploinsufficiency is not enough to produce the phenotype of Emberger syndrome. It could be useful to perform whole exome or genome sequencing, in cases where incomplete penetrance or high variable expressivity is described, in order to probably identify specific gene interactions that drastically modify the phenotype. In addition, skewed gene expression by an epigenetic mechanism of gene regulation should also be considered.
authors.affiliation: a Departamento de Psicología Básica , Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara , Guadalajara , Jalisco , México.
authors.forename: Aniel Jessica Leticia
authors.identifier: http://orcid.org/0000-0002-6455-3662
authors.initials: AJL
authors.lastname: Brambila-Tapia
authors.affiliation: b División de Genética, Centro de Investigación Biomédica de Occidente (CIBO) , Instituto Mexicano del Seguro Social (IMSS) , Guadalajara , Jalisco , México.
authors.forename: José Elías
authors.identifier: http://orcid.org/0000-0003-1504-1457
authors.initials: JE
authors.lastname: García-Ortiz
authors.affiliation: c Human Molecular Genetics , de Duve Institute, Université catholique de Louvain , Brussels , Belgium.
authors.forename: Pascal
authors.identifier: http://orcid.org/0000-0001-9548-8229
authors.initials: P
authors.lastname: Brouillard
authors.affiliation: c Human Molecular Genetics , de Duve Institute, Université catholique de Louvain , Brussels , Belgium.
authors.forename: Ha-Long
authors.identifier: http://orcid.org/0000-0002-4976-1615
authors.initials: HL
authors.lastname: Nguyen
authors.affiliation: c Human Molecular Genetics , de Duve Institute, Université catholique de Louvain , Brussels , Belgium.|d Walloon Excellence in Life sciences and Biotechnology (WELBIO) , Université catholique de Louvain , Brussels , Belgium.
authors.forename: Miikka
authors.identifier: http://orcid.org/0000-0002-6236-338X
authors.initials: M
authors.lastname: Vikkula
authors.affiliation: e Unidad Médico Familiar #34 , Instituto Mexicano del Seguro Social (IMSS) , Guadalajara , Jalisco , México.
authors.forename: Blanca Estela
authors.identifier: http://orcid.org/0000-0001-8197-455X
authors.initials: BE
authors.lastname: Ríos-González
authors.affiliation: f Doctorado en Genética Humana, Centro Universitario de Ciencias de la Salud (CUCS) , Universidad de Guadalajara , Guadalajara , Jalisco , México.
authors.forename: Roberto de Jesús
authors.identifier: http://orcid.org/0000-0001-7111-1793
authors.initials: RJ
authors.lastname: Sandoval-Muñiz
authors.affiliation: f Doctorado en Genética Humana, Centro Universitario de Ciencias de la Salud (CUCS) , Universidad de Guadalajara , Guadalajara , Jalisco , México.
authors.forename: Ana Karen
authors.identifier: http://orcid.org/0000-0002-2702-5625
authors.initials: AK
authors.lastname: Sandoval-Talamantes
authors.affiliation: f Doctorado en Genética Humana, Centro Universitario de Ciencias de la Salud (CUCS) , Universidad de Guadalajara , Guadalajara , Jalisco , México.|g Departamento de Biología Molecular y Genómica , Instituto de Genética Humana, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara , Guadalajara , Jalisco , México.
authors.forename: Lucina
authors.identifier: http://orcid.org/0000-0001-7324-2287
authors.initials: L
authors.lastname: Bobadilla-Morales
authors.affiliation: f Doctorado en Genética Humana, Centro Universitario de Ciencias de la Salud (CUCS) , Universidad de Guadalajara , Guadalajara , Jalisco , México.|g Departamento de Biología Molecular y Genómica , Instituto de Genética Humana, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara , Guadalajara , Jalisco , México.|h Servicio de Genética, División de Pediatría , Hospital Civil de Guadalajara, 'Dr. Juan I. Menchaca' , Guadalajara , Jalisco , México.
authors.forename: Jorge Román
authors.identifier: http://orcid.org/0000-0001-7968-2267
authors.initials: JR
authors.lastname: Corona-Rivera
authors.affiliation: h Servicio de Genética, División de Pediatría , Hospital Civil de Guadalajara, 'Dr. Juan I. Menchaca' , Guadalajara , Jalisco , México.
authors.forename: Lisette
authors.identifier: http://orcid.org/0000-0002-3681-6365
authors.initials: L
authors.lastname: Arnaud-Lopez
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D050989:GATA2 Transcription Factor / Q000235:genetics*; D056726:Genetic Association Studies; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D019683:Penetrance; D010641:Phenotype; D013577:Syndrome
chemical_list: D050989:GATA2 Transcription Factor
keywords: Emberger syndrome; GATA-2 mutations; incomplete penetrance