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Novel G6PC3 Mutations in Patients with Congenital Neutropenia: Case Reports and Review of the Literature

Author(s):

Seyed Farzad Maroufi, Zoha Shaka, Helia Mojtabavi, Mona Sadeghalvad, Elham Rayzan, Iraj Sedighi, Sepideh Shahkarami, Mehri Najafi, Meino Rohlfs, Christoph Klein and Nima Rezaei*   Pages 1 - 9 ( 9 )

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, and it 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 and 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 has not been reported in the G6PDC3 gene.

Conclusions: 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.

Keywords:

severe congenital neutropenia, glucose-6-phosphatase catalytic subunit 3, immunodeficiency, SCN4, G6PC3, case report

Affiliation:

Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, International Hematology/Oncology of Pediatrics Experts (IHOPE), Universal Scientific Education and Research Network (USERN), Tehran, Department of Pediatrics, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, IR , Medical Genetics Network (MeGeNe), Universal Scientific Education and Research Network (USERN), Munich, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, Munich, Department of Pediatric Gastroenterology, Children’s Hospital Medical Center, Tehran University of Medical Sciences, Tehran, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, Munich, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, Munich, Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran



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