Premium
Resolving a genetic paradox throughout preimplantation genetic diagnosis for autosomal dominant severe congenital neutropenia
Author(s) -
Malcov Mira,
Reches Adi,
BenYosef Dalit,
Cohen Tania,
Amit Ami,
Dgany Orly,
Tamary Hannah,
Yaron Yuval
Publication year - 2010
Publication title -
prenatal diagnosis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.956
H-Index - 97
eISSN - 1097-0223
pISSN - 0197-3851
DOI - 10.1002/pd.2437
Subject(s) - biology , congenital neutropenia , haplotype , germline mosaicism , preimplantation genetic diagnosis , genetics , sperm , mutation , immunology , bone marrow , allele , pregnancy , gene
Objective Severe congenital neutropenia is an inherited disease characterized by low peripheral blood neutrophils, amenable to bone marrow transplantation. Genetic analysis in the family here described detected a ELA2 splice‐site mutation in the affected child and also in his asymptomatic father. The parents requested preimplantation genetic diagnosis (PGD), coupled with HLA matching, to obtain a suitable bone marrow donor for the affected child. Methods A PGD protocol was developed, based on multiplex nested PCR for direct analysis of the ELA2 mutation, flanking polymorphic markers and HLA typing. Results The amplification efficiency of the mutation was > 90% in single leukocytes from the affected child but only 67% in the father. Analysis of single haploid sperm cells from the father demonstrated three different sperm‐cell populations: (1) sperm cells harboring the ELA2 mutation on the ‘affected’ haplotype, (2) sperm cells without the ELA2 mutation on the ‘normal’ haplotype, and (3) sperm cells without the ELA2 mutation on the ‘affected’ haplotype. Conclusion These data demonstrate that the ELA2 mutation in the father occurred de novo during his embryonic development, resulting in somatic as well as germ‐line mosaicism. This conclusion was also taken into consideration when PGD was performed. Copyright © 2010 John Wiley & Sons, Ltd.