Cyclic neutropenia and severe congenital neutropenia in patients with a shared ELANE mutation and paternal haplotype: evidence for phenotype determination by modifying genes
Authors
Newburger, Peter E.Pindyck, Talia N.
Zhu, Zhiqing
Bolyard, Audrey Anna
Aprikyan, Andrew A.G.
Dale, David C.
Smith, Gary D.
Boxer, Laurence A.
Document Type
Journal ArticlePublication Date
2010-08-01Keywords
Base SequenceChild
Child, Preschool
Fathers
Genetic Predisposition to Disease
*Haplotypes
Humans
Infant
Inheritance Patterns
Leukocyte Elastase
Male
*Mutation
Neutropenia
Pedigree
Phenotype
Spermatozoa
Hematology
Oncology
Pediatrics
Metadata
Show full item recordAbstract
BACKGROUND: Cyclic neutropenia (CN) and severe congenital neutropenia (SCN) are disorders of neutrophil production that differ markedly in disease severity. Mutations of the ELANE gene (the symbol recently replacing ELA2) are considered largely responsible for most cases of CN and SCN, but specific mutations are typically associated with one or the other. PROCEDURE: We performed ELANE genotyping on all individuals and paternal sperm in an SCN kindred with eight SCN progeny of a sperm donor and six different mothers. RESULTS: One patient with CN had the same S97L ELANE mutation as seven patients with the SCN phenotype. The mutant allele was detected in the donor's spermatozoa, representing 18% of the ELANE gene pool, but not in DNA from his lymphocytes, neutrophils, or buccal mucosa, indicating gonadal mosaicism. CONCLUSIONS: The coexistence of CN and SCN phenotypes in this kindred with a shared paternal haplotype strongly suggests both a role for modifying genes in determination of congenital neutropenia disease phenotypes, and the classification of CN and SCN within a spectrum of phenotypes expressing varying degrees of the same disease process.Source
Pediatr Blood Cancer. 2010 Aug;55(2):314-7. Link to article on publisher's websiteDOI
10.1002/pbc.22537Permanent Link to this Item
http://hdl.handle.net/20.500.14038/43328PubMed ID
20582973Notes
Talia Pindyck participated in this study as a medical student as part of the Senior Scholars research program at the University of Massachusetts Medical School.
Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1002/pbc.22537