title: G6PC3 mutations cause non-syndromic severe congenital neutropenia.
abstract: The deficiency of ubiquitously expressed glucose-6-phosphatase (G6PC3) enzyme is known to result in a syndrome characterized by severe congenital neutropenia, prominent superficial venous pattern, congenital heart defects and genito-urinary malformations. Here, we describe four patients from three families with non-syndromic severe congenital neutropenia and identify four G6PC3 mutations as causative in these cases. Thus we demonstrate that G6PC3 mutations also result in a non-syndromic form of severe congenital neutropenia. We propose that G6PC3 deficiency should be considered as part of the differential diagnoses in any patient with unexplained congenital neutropenia. Additionally, we show a relationship between the genotype and non-hematological phenotype of G6PC3 deficiency. These findings may provide an insight into the role of the G6PC3 enzyme and glucose metabolism in developmental pathways.
authors.affiliation: Genetic Medicine, St Mary's Hospital, Manchester Academic Health Sciences Centre, University of Manchester, and St Mary's Hospital, Manchester, M13 9WL, UK. Siddharth.Banka@manchester.ac.uk
authors.forename: Siddharth
authors.initials: S
authors.lastname: Banka
authors.forename: Robert
authors.initials: R
authors.lastname: Wynn
authors.forename: Helen
authors.initials: H
authors.lastname: Byers
authors.forename: Peter D
authors.initials: PD
authors.lastname: Arkwright
authors.forename: William G
authors.initials: WG
authors.lastname: Newman
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D000080984:Congenital Bone Marrow Failure Syndromes; D005091:Exons; D005260:Female; D005838:Genotype; D005952:Glucose-6-Phosphatase / Q000235:genetics*; D006801:Humans; D009154:Mutation; D009503:Neutropenia / Q000151:congenital* / Q000235:genetics; D016415:Sequence Alignment
chemical_list: D005952:Glucose-6-Phosphatase; C492193:G6PC3 protein, human