Person et al. (2003) identified a heterozygous mutation in the GFI1 gene (600871.0001; see MOLECULAR GENETICS) in a 4-month-old boy with SCN2 who had a neutrophil count of zero and marked monocytosis. The mutation segregated with his 3-year-old ... Person et al. (2003) identified a heterozygous mutation in the GFI1 gene (600871.0001; see MOLECULAR GENETICS) in a 4-month-old boy with SCN2 who had a neutrophil count of zero and marked monocytosis. The mutation segregated with his 3-year-old paternal half brother, who was identically affected, and with their father, who had recurrent pneumonia and pyogenic abscesses abating during childhood. The father's childhood blood counts were not available, but at age 27 his neutrophil count was low and monocytes high. His peripheral blood showed a population of myeloid cells that appeared immature. The myeloid, but not erythroid, colony formation potential of his cultured peripheral blood was lower than normal; nonerythroid colonies had intact differentiation to monocytes or macrophages but had an excess of myeloid precursors with no mature neutrophils. The absolute cell number of CD4 T lymphocytes was reduced. Moreover, B lymphocytes were also reduced. Peripheral blood lymphocytes from both the father and the older son showed similar trends, and both had poor uptake of 3H-thymidine after stimulation with phytohemagglutinin, alloantigen, and Candida albicans compared with normal individuals. Nonetheless, the child had adequate circulating titers to immunizations, and all immunoglobulin isotypes were present in his serum, indicating that, though reduced in number and activation potential, the T and B lymphocyte populations were functional.
Person et al. (2003) screened GFI1 as a candidate for association with neutropenia in individuals without mutations in ELA2 (130130), the most common cause of autosomal dominant severe congenital neutropenia (SCN1; 202700). They identified a dominant-negative zinc finger ... Person et al. (2003) screened GFI1 as a candidate for association with neutropenia in individuals without mutations in ELA2 (130130), the most common cause of autosomal dominant severe congenital neutropenia (SCN1; 202700). They identified a dominant-negative zinc finger mutation (600871.0003) in individuals with SCN2 that disabled transcriptional repressor activity. They showed by chromatin immunoprecipitation, gel shift, reporter assays, and elevated expression of ELA2 in vivo in neutropenic individuals that GFI1 represses ELA2, thus linking these 2 genes in a common pathway involved in myeloid differentiation.