GATA2 null mutation associated with incomplete penetrance in a family with Emberger syndrome

Introduction: 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 (5 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 (2 of which were deceased) while 2 remained unaffected at the age of 40 and 13 years old. The three affected siblings (2 boys and 1 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. Discussion: Incomplete penetrance may indicate that GATA2 haploinsufficiency is not enough to produce the phenotype of Emberger syndrome. Therefore, in cases where incomplete penetrance or high variable expressivity is described, whole exome or genome sequencing would be useful in order to 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

Compilación de Proyectos de Investigación desde el año 2003 al 2012

Listado de Proyectos de investigación de UPIICSA desde 2003 a 201