A Novel Homozygous Mutation in G6PC3 Presenting as Cyclic Neutropenia and Severe Congenital Neutropenia in the Same Family

• Published in: Journal of clinical immunology Vol. 33; no. 8; pp. 1403 - 1406
• Main Authors: Alangari, Abdullah A., Alsultan, Abdulrahman, Osman, Mohamed Elfaki, Anazi, Shamsa, Alkuraya, Fowzan S.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01-11-2013; Springer Nature B.V
• Subjects: Biomedical and Life Sciences; Biomedicine; Brief Communication; Child; Genes, Recessive; Glucose-6-Phosphatase - genetics; Homozygote; Humans; Immunology; Infectious Diseases; Internal Medicine; Male; Medical Microbiology; Mutation; Neutropenia - diagnosis; Neutropenia - genetics; Neutropenia - immunology; Pedigree; Phenotype; Severity of Illness Index; congenital heart disease; G6PC3; autozygosity mapping; thrombocytopenia; severe congenital neutropenia; Cyclic neutropenia
• ISSN: 0271-9142; 1573-2592
• DOI: 10.1007/s10875-013-9945-7

Purpose
Patients with autosomal recessive cyclic neutropenia have no known causative genetic defect yet.
Methods
Autozygosity mapping on two branches of an extended multiplex consanguineous family presenting with cyclic neutropenia or severe congenital neutropenia to look for candidate gene, followed by candidate gene selection and sequencing.
Results
A single autozygous interval on Chr17:33,901,938-45,675,414 that is exclusively shared by the affected members was identified. This interval spans 11.8 Mb and contains 30 genes. Review of these genes highlighted
G6PC3
as the most likely candidate given its known role in neutrophil biology. Direct sequencing revealed a novel homozygous mutation (NM_138387.3, c.974T > G, p.Leu325Arg). Two of our patients had associated congenital defects that are known to occur in patients with
G6PC3
mutations, including congenital heart disease and intermittent thrombocytopenia.
Conclusion
Biallelic
G6PC3
defects should be considered in patients with autosomal recessive cyclic neutropenia, especially those with typical associated congenital defects.