title: Phenotypic Heterogeneity of Neutropenia and Gastrointestinal Illness Associated with G6PC3 Founder Mutation.
abstract: Severe congenital neutropenia type IV (SCN IV) is a syndrome of severe neutropenia, cardiac and urogenital defects, prominent superficial veins, facial dysmorphism, failure to thrive (FTT), and intermittent thrombocytopenia, caused by a glucose-6-phosphatase catalytic subunit 3 (G6PC3) gene mutation. SCN IV has been linked to glycogen storage disease type 1b as both disorders involve disruption of the glucose-6-phosphatase/glucose-6-phosphate transporter complex, leading to arrested neutrophil maturation. Emerging evidence suggests that neutrophil function plays an important role in intestinal integrity, evidenced by inflammatory bowel disease in certain neutropenic patients. Here, we report 3 unrelated Hispanic males from the Dominican Republic with classic features of SCN IV found to share an identical inherited canonical splice-site mutation of the G6PC3 gene (c.218+1G>A). All 3 patients presented with severe FTT and gastrointestinal manifestations. Two of the patients had significant improvement in growth and resolution of gastrointestional symptoms with initiation of granulocyte colony-stimulating factor. We hypothesize that the gene variant described represents a founder mutation in the Dominican Republic, the first to be described in this geographical region. We discuss the potential associations between neutropenia and gastrointestinal disease with FTT and the role of granulocyte colony-stimulating factor in improving neutrophil count and intestinal integrity and growth.
authors: *Department of Pediatric Hematology/Oncology, Winthrop University Medical Center, Mineola †Division of Pediatric Gastroenterology, Hepatology, and Nutrition Departments of §Pediatric Hematology, Oncology and Stem Cell Transplantation ‡Pathology, Cell Biology, and Personalized Genomic Medicine ∥Pediatrics, Division of Clinical Genetics, Columbia University Medical center, New York, NY.
authors: Chana L
authors: CL
authors: Glasser
authors: Joseph A
authors: JA
authors: Picoraro
authors: Preti
authors: P
authors: Jain
authors: Sivan
authors: S
authors: Kinberg
authors: Evelyn
authors: E
authors: Rustia
authors: Kara
authors: K
authors: Gross Margolis
authors: Kwame
authors: K
authors: Anyane-Yeboa
authors: Alejandro D
authors: AD
authors: Iglesias
authors: Nancy S
authors: NS
authors: Green
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D000080984:Congenital Bone Marrow Failure Syndromes; D005183:Failure to Thrive / Q000209:etiology; D005767:Gastrointestinal Diseases / Q000235:genetics*; D005952:Glucose-6-Phosphatase / Q000235:genetics*; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D008297:Male; D009154:Mutation; D009503:Neutropenia / Q000151:congenital* / Q000188:drug therapy / Q000235:genetics; D010641:Phenotype
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D005952:Glucose-6-Phosphatase; C492193:G6PC3 protein, human