Boxer Laurence A, Stein Steven, Buckley Danielle, Bolyard Audrey Anna, Dale David C
Divison of Pediatric Hematology/Oncology, Department of Pediatrics, C.S. Mott Children's Hospital, University of Michigan, Ann Arbor, Michigan 48109-0238, USA.
J Pediatr. 2006 May;148(5):633-6. doi: 10.1016/j.jpeds.2005.12.029.
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.
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.
None of the mothers 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 on chromosome 19, which contains ELA2.
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.
调查严重先天性中性粒细胞减少症（SCN）病例，在确定4个不同家庭使用同一精子供体使母亲受孕后，确定SCN的遗传情况。
由于无法获得供体精子，采用替代方法来确定精子供体是否传递了SCN。从白细胞中分离的DNA用于对患病儿童及其母亲的ELA2基因进行测序。通过聚合酶链反应（PCR）扩增ELA2，并对产物进行测序。还使用一组位于14号和19号染色体上的22个微卫星PCR引物，对母亲和患病儿童的基因组DNA进行PCR，以建立与父本等位基因的连锁关系。
母亲中均未检测到ELA2突变，但所有５名患病儿童均有相同的突变，影响第4外显子的S97L位点。连锁图谱分析证实，所有患病儿童在包含ELA2的19号染色体上具有相同的父本等位基因。
我们的研究结果表明，父亲提供了一致的单倍型，导致所有患病儿童中SCN的表达，支持ELA2突变的常染色体显性遗传。
