From OMIMSevere congenital neutropenia is a heterogeneous disorder of hematopoiesis characterized by a maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10(9)/l and early onset of severe bacterial infections (Skokowa et al., 2007). About 60% of affected individuals of European and Middle Eastern ancestry have dominant ELANE mutations, resulting in a form of severe congenital neutropenia, which is designated here as SCN1.
Genetic Heterogeneity of Severe Congenital Neutropenia
Severe congenital neutropenia is a genetically heterogeneous disorder showing autosomal dominant, autosomal recessive, and X-linked inheritance. Other autosomal dominant forms are SCN2 (613107), caused by mutation in the protooncogene GFI1 (600871) on 1p22; SCN8 (618752), caused by mutation in the SRP54 gene (604857) on 14q13; SCN9 (619813), caused by mutation in the CLPB gene (616254) on 11q13; and SCN11 (620674), caused by mutation in the SEC61A1 gene (609213) on chromosome 3q21.
Autosomal recessive forms include SCN3 (610738), caused by mutation in the HAX1 gene (605998) on 1q21; SCN4 (612541), caused by mutation in the G6PC3 gene (611045) on 17q21; SCN5 (615285), caused by mutation in the VPS45 gene (610035) on 1q21; SCN6 (616022), caused by mutation in the JAGN1 gene (616012) on 3p25; SCN7 (617014), caused by mutation in the CSF3R gene (138971) on 1p34; and SCN10 (620534), caused by mutation in the SRP68 gene (604858) on chromosome 17q25.
X-linked SCN (SCNX; 300299) is caused by mutation in the WAS gene (300392) on Xp11.
See also adult chronic idiopathic nonimmune neutropenia (607847) and chronic benign familial neutropenia (162700).
Susceptibility to Myelodysplastic Syndrome/Acute Myeloid Leukemia
SCN patients with acquired mutations in the granulocyte colony-stimulating factor receptor (CSF3R; 138971) in hematopoietic cells define a group with high risk for progression to myelodysplastic syndrome and/or acute myeloid leukemia. Approximately 80% of SCN patients who develop AML are heterozygous for somatic CSF3R mutations (summary by Klimiankou et al., 2016).
http://www.omim.org/entry/202700