由ELA2突变导致的严重先天性中性粒细胞减少症为常染色体显性遗传病的有力证据

• 作 者: Boxer L.A. Stein S. Buckley D. 贺莉
• 机 构: Divison of Pediatric Hematology/Oncology Department of Pediatrics,C.S. Mott Children's Hospital,Ann
• 出 处: 世界核心医学期刊文摘(儿科学分册)
• 发表日期: 2006年12期
• 关键词: ELA2 同源染色体 精子 聚合酶链反应 父方 等位基因 基因序列 供体 碱基 单倍体

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 primerson chromosomes 14 and 19 to establish linkage to the paternalallele. Results: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. 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.

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 DNA from leukocytes was used to sequence the 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 paternalallele. Results: None of the mothers had a mutation in ELA2, but all 5 affected children had the same mutation affect 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. Conclusi ons: 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.