Title:Novel G6PC3 Mutations in Patients with Congenital Neutropenia: Case Reports and Review of the Literature
Volume: 21
Issue: 9
Author(s): Seyed F. Maroufi, Zoha Shaka, Helia Mojtabavi, Mona Sadeghalvad, Elham Rayzan, Iraj Sedighi, Sepideh Shahkarami, Mehri Najafi, Meino Rohlfs, Christoph Klein and Nima Rezaei*
Affiliation:
- Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran,Iran
Keywords:
Severe congenital neutropenia, glucose-6-phosphatase catalytic subunit 3, immunodeficiency, SCN4, G6PC3,
case report.
Abstract:
Background: Severe congenital neutropenia (SCN4) caused by mutations in glucose-6-
phosphatase catalytic subunit 3 (G6PC3) is characterized by recurrent infections due to severe neutropenia,
may be accompanied by other extra-hematopoietic manifestations; including structural heart
defects, urogenital abnormalities, prominent superficial venous markings, growth retention, and inflammatory
bowel diseases with rare incidence. The homozygous or compound heterozygous mutations
of G6PC3 are responsible for most cases of autosomal recessive SCN4. Herein, we present two
cases of SCN4 affected by novel mutations in the G6PC3, in addition to a summarized list of variants
in G6PC3 gene that are reported as pathogenic and related to the SCN4 phenotype.
Case Presentation: Herein, we present two cases of SCN4; the first case was a three-months old boy
with severe neutropenia and prior history of hospitalization due to umbilical separation, umbilical herniation,
omphalitis, and pyelonephritis; and the second case was an eight-year-old with a history of
neutropenia, recurrent and severe episodes of intractable diarrhea, refractory rectovaginal and rectoperineal
fistula, congenital inguinal hernia, and ASD type 2. Whole exome sequencing was performed for
both cases, which revealed two novel homozygous missense mutations in G6PC3 that were predicted
to be deleterious; c.337G>A, p. Gly113Arg in the first case and c.479C>T; P. Ser160Leu in the second
case. To our knowledge, both of these two mutations have not been reported in the G6PDC3 gene.
Conclusion: In patients with severe neutropenia with varying extra hematopoietic syndrome, mutation
of G6PC3 should be suspected after ruling out other mutations related to neutropenia. This study
pointed toward novel G6PC3 mutations that should be considered in order to diagnose patients with
severe congenital neutropenia.
