A novel phenotype variant of severe congenital neutropenia caused by G6PC3 deficiency

Area of Science:

• Genetics and Molecular Biology
• Hematology
• Pediatric Cardiology

Background:

• Severe congenital neutropenia type 4 (SCN4) is a genetic disorder caused by G6PC3 gene mutations.
• The p.Gly260Arg variant of G6PC3 has been consistently associated with cardiac anomalies in previous studies.
• Understanding the phenotypic variability of SCN4 is crucial for accurate diagnosis and management.

Purpose of the Study:

• To report a case of SCN4 with the p.Gly260Arg G6PC3 variant presenting without cardiac defects.
• To evaluate the efficacy of granulocyte colony-stimulating factor (G-CSF) in managing neutropenia and neutrophil dysfunction in this patient.
• To contribute to the understanding of genotype-phenotype correlations in G6PC3-associated neutropenia.

Main Methods:

• Genetic sequencing to identify the G6PC3 mutation.
• Comprehensive echocardiography and cardiac function assessment.
• Clinical monitoring of neutrophil counts and function.
• Treatment with G-CSF and assessment of therapeutic response.

Main Results:

• A patient with the p.Gly260Arg G6PC3 variant was identified without structural or functional heart anomalies.
• Treatment with G-CSF successfully normalized absolute neutrophil count.
• Neutrophil functional competence was restored following G-CSF therapy.
• This case expands the known clinical spectrum of G6PC3-related SCN4.

Conclusions:

• The p.Gly260Arg G6PC3 variant does not invariably lead to cardiac defects in SCN4.
• G-CSF is an effective treatment for neutropenia and neutrophil dysfunction in SCN4 patients with this variant.
• Further research is needed to elucidate the factors influencing cardiac involvement in G6PC3 mutations.