title: Resolving a genetic paradox throughout preimplantation genetic diagnosis for autosomal dominant severe congenital neutropenia.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Sara Racine in vitro Fertilization Unit, Lis Maternity Hospital, Tel Aviv, Israel.
authors.forename: Mira
authors.initials: M
authors.lastname: Malcov
authors.forename: Adi
authors.initials: A
authors.lastname: Reches
authors.forename: Dalit
authors.initials: D
authors.lastname: Ben-Yosef
authors.forename: Tania
authors.initials: T
authors.lastname: Cohen
authors.forename: Ami
authors.initials: A
authors.lastname: Amit
authors.forename: Orly
authors.initials: O
authors.lastname: Dgany
authors.forename: Hannah
authors.initials: H
authors.lastname: Tamary
authors.forename: Yuval
authors.initials: Y
authors.lastname: Yaron
mesh_terms: D004252:DNA Mutational Analysis; D000075065:Elongin; D005192:Family Health; D005220:Fathers; D005260:Female; D005307:Fertilization in Vitro; D005799:Genes, Dominant; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D009154:Mutation; D009503:Neutropenia / Q000151:congenital* / Q000235:genetics*; D009504:Neutrophils / Q000473:pathology; D010375:Pedigree; D019836:Preimplantation Diagnosis / Q000379:methods*; D022821:RNA Splice Sites / Q000235:genetics; D013094:Spermatozoa / Q000737:chemistry; D014157:Transcription Factors / Q000235:genetics
chemical_list: D000075065:Elongin; D022821:RNA Splice Sites; D014157:Transcription Factors