Mosaicism of an ELANE Mutation in an Asymptomatic Mother View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-01

AUTHORS

Tomonari Shigemura, Norimoto Kobayashi, Kazunaga Agematsu, Osamu Ohara, Yozo Nakazawa

ABSTRACT

PURPOSE: We report normal neutrophil count in a mother, who carries the same ELANE mutation as her daughter with severe congenital neutropenia. We hypothesized that the mother possessed wild- and mutant-type clones and the wild-type clones could generate neutrophils, whereas the mutant clones could not. METHODS: We confirmed mutant variant ratio by sequence signals and measured the frequency of the mutant allele by subcloning in various cell types. We established the ELANE-mutated and non-mutated induced pluripotent stem cells (iPSCs) from the mother's T cells and compared granulopoiesis between these iPSCs. RESULTS: In the sequence analysis of isolated peripheral blood (PB), nail and hair, the mutant variant was detected in approximately 40-60% of lymphocytes, monocytes, hematopoietic progenitor cells, and hair as well as in a small percentage of nail, but in none of the neutrophils. In the subcloning analysis of extracted DNA from CD3+ and CD34+ cells, the mutant allele was identified in 37.5% and 38.1%, respectively. We reprogrammed the mother's PB cells and established the ELANE-mutated and non-mutated iPSCs. Granulopoiesis from mutated iPSCs revealed little sensitivity to granulocyte colony-stimulating factor in comparison with non-mutated iPSCs. CONCLUSIONS: These observations strongly suggest that mutant-carrying neutrophils did not appear in the mother's PB because mutated clones could not differentiate into neutrophils. The mother's normal hematological phenotype could be explained by the perseverance of normal, non-mutated granulopoiesis. More... »

PAGES

106-111

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s10875-018-0580-1

DOI

http://dx.doi.org/10.1007/s10875-018-0580-1

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1111363423

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30635825


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