Strong evidence for autosomal dominant inheritance of severe congenital neutropenia associated with ELA2 mutations

Objective To investigate cases of severe congenital neutropenia (SCN) to ascertain SCN inheritance after determining that the same sperm donor was used by 4 different families to impregnate mothers. Study design Because the donor sperm was not available, alternative methods were used to determine whether the sperm donor transmitted SCN. DNA isolated from leukocytes was used to sequence the ELA2 gene in the affected children and their mothers. ELA2 was amplified by polymerase chain reaction (PCR), and the product was sequenced. PCR was also performed with genomic DNA from the mothers and affected children using a set of 22 microsatellite PCR primers on chromosomes 14 and 19 to establish linkage to the paternal allele. Results None of the in others had a mutation in ELA2, but all 5 affected children had the same mutation affecting the fourth exon at site S97L. Linkage mapping analysis confirmed that all affected children had the same paternal allele oil chromosome 19. which contains ELA2. Conclusions Our findings indicate that the father provided consistent haplotypes leading to the expression of SCN in all affected children. supporting an autosomal dominant inheritance in which ELA2 mutations occur.