title: Extended spectrum of human glucose-6-phosphatase catalytic subunit 3 deficiency: novel genotypes and phenotypic variability in severe congenital neutropenia.
abstract: OBJECTIVE
  To delineate the phenotypic and molecular spectrum of patients with a syndromic variant of severe congenital neutropenia (SCN) due to mutations in the gene encoding glucose-6-phosphatase catalytic subunit 3 (G6PC3).
  
  
  METHODS
  Patients with syndromic SCN were characterized for associated malformations and referred to us for G6PC3 mutational analysis.
  
  
  RESULTS
  In a cohort of 31 patients with syndromic SCN, we identified 16 patients with G6PC3 deficiency including 11 patients with novel biallelic mutations. We show that nonhematologic features of G6PC3 deficiency are good predictive indicators for mutations in G6PC3. Additionally, we demonstrate genetic variability in this disease and define novel features such as growth hormone deficiency, genital malformations, disrupted bone remodeling, and abnormalities of the integument. G6PC3 mutations may be associated with hydronephrosis or facial dysmorphism. The risk of transition to myelodysplastic syndrome/acute myeloid leukemia may be lower than in other genetically defined SCN subgroups.
  
  
  CONCLUSIONS
  The phenotypic and molecular spectrum in G6PC3 deficiency is wider than previously appreciated. The risk of transition to myelodysplastic syndrome or acute myeloid leukemia may be lower in G6PC3 deficiency compared with other subgroups of SCN.
authors: Research Center for Molecular Medicine of the Austrian Academy of Sciences (CeMM), Vienna, Austria. kboztug@cemm.oeaw.ac.at
authors: Kaan
authors: K
authors: Boztug
authors: Philip S
authors: PS
authors: Rosenberg
authors: Marie
authors: M
authors: Dorda
authors: Siddharth
authors: S
authors: Banka
authors: Thomas
authors: T
authors: Moulton
authors: Julie
authors: J
authors: Curtin
authors: Nima
authors: N
authors: Rezaei
authors: John
authors: J
authors: Corns
authors: Jeffrey W
authors: JW
authors: Innis
authors: Zekai
authors: Z
authors: Avci
authors: Hung Chi
authors: HC
authors: Tran
authors: Isabelle
authors: I
authors: Pellier
authors: Paolo
authors: P
authors: Pierani
authors: Rachel
authors: R
authors: Fruge
authors: Nima
authors: N
authors: Parvaneh
authors: Setareh
authors: S
authors: Mamishi
authors: Rajen
authors: R
authors: Mody
authors: Phil
authors: P
authors: Darbyshire
authors: Jayashree
authors: J
authors: Motwani
authors: Jennie
authors: J
authors: Murray
authors: George R
authors: GR
authors: Buchanan
authors: William G
authors: WG
authors: Newman
authors: Blanche P
authors: BP
authors: Alter
authors: Laurence A
authors: LA
authors: Boxer
authors: Jean
authors: J
authors: Donadieu
authors: Karl
authors: K
authors: Welte
authors: Christoph
authors: C
authors: Klein
mesh_terms: D000293:Adolescent; D002648:Child; D000080984:Congenital Bone Marrow Failure Syndromes; D005260:Female; D005838:Genotype; D005952:Glucose-6-Phosphatase / Q000235:genetics*; D005953:Glycogen Storage Disease Type I / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D009503:Neutropenia / Q000151:congenital* / Q000235:genetics; D010641:Phenotype
chemical_list: D005952:Glucose-6-Phosphatase; C492193:G6PC3 protein, human