The diversity of mutations and clinical outcomes for ELANE-associated neutropenia
Authors
Makaryan, VahagnZeidler, Cornelia
Bolyard, Audrey Anna.
Skokowa, Julia
Rodger, Elin
Kelley, Merideth L.
Boxer, Laurence A.
Bonilla, Mary Ann.
Shimamura, Akiko
Zhu, Bin
Rosenberg, Philip S.
Link, Daniel C.
Welte, Karl
Dale, David C.
Newburger, Peter E.
UMass Chan Affiliations
Department of Pediatrics, Division of Hematology/OncologyDocument Type
Journal ArticlePublication Date
2015-01-01
Metadata
Show full item recordAbstract
PURPOSE OF REVIEW: Mutations in the gene for neutrophil elastase, ELANE, cause cyclic neutropenia (CyN) and severe congenital neutropenia (SCN). This study summarized data from the Severe Chronic Neutropenia International Registry (SCNIR) on genotype-phenotype relationships of ELANE mutations to important clinical outcomes. We also summarize findings for ELANE mutations not observed in SCNIR patients. RECENT FINDINGS: There were 307 SCNIR patients with 104 distinctive ELANE mutations who were followed longitudinally for up to 27 years. The ELANE mutations were diverse; there were 65 single amino acid substitutions; 61 of these mutations (94%) were 'probably' or 'possibly damaging' by PolyPhen-2 analysis, and one of the 'benign' mutations was associated with two cases of acute myeloid leukemia (AML). All frame-shift mutations (19/19) were associated with the SCN. The pattern of mutations in the SCN versus CyN was significantly different (P < 10), but some mutations were observed in both groups (overlapping mutations). The cumulative incidence of severe adverse events, that is, myelodysplasia, AML, stem cell transplantation, or deaths was significantly greater for patients with SCN versus those with CyN or overlapping mutations. Specific mutations (i.e. G214R or C151Y) had a high risk for evolution to AML. SUMMARY: Sequencing is useful for predicting outcomes of ELANE-associated neutropenia.Source
Curr Opin Hematol. 2015 Jan;22(1):3-11. doi: 10.1097/MOH.0000000000000105. Link to article on publisher's siteDOI
10.1097/MOH.0000000000000105Permanent Link to this Item
http://hdl.handle.net/20.500.14038/43724PubMed ID
25427142Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1097/MOH.0000000000000105