关键词: 先天性中性粒细胞减少；　Cohen综合征；　VPS13B基因；　CSF3R基因

Abstract: Objective　To explore the clinical and gene mutation characteristics of rare severe congenital neutropenia. Method　The clinical data of severe congenital neutropenia in 2 children diagnosed by gene detection were analyzed retrospectively, and the relevant literature was reviewed. Results　Two children, one boy aged 1 year and 9 months and one girl aged 2 years old, had a history of recurrent infection. The boy’s lowest absolute neutrophil count (ANC) was 0.17×109/ L, accompanied by developmental abnormalities. The whole exon gene detection showed two heterozygous mutations in VPS13B gene, a frameshift mutation, c.8531delG (p.sper2844fs), in Exon47 from the father and the intron mutation of intron 38(c.6940+1G>T) from the mother. In Combination with the clinical manifestations, the boy was diagnosed with Cohen's syndrome. The girl’s ANC fluctuated around 0.4 × 109 / L for a long time. The whole exon gene detection revealed two heterozygous mutations in CSF3R gene, the intron mutations of intron3 (c.64+5G>A) from the father, and a frameshift mutation c.690delC (p.Met231Cysfs *32) in Exon7 from the mother. In combination with clinical manifestations, the girl was considered to have severe congenital neutropenia type 7 (SCN7). The treatment of granulocyte colony-stimulating factor (G-GSF) was ineffective, but granulocyte macrophage colony stimulating factor (GM-CSF) was effective. Conclusions　Severe congenital neutropenia can lead to severe or recurrent infections, which are the characteristic manifestations of certain syndromes. Some children may change to myelodysplastic syndrome or acute myeloid leukemia, requiring long-term follow-up and treatment. Genetic testing is helpful for diagnosis.

Key words: 　congenital neutropenia;　Cohen syndrome;　VPS13B gene;　CSF3R gene