Cyclic neutropenia and severe congenital neutropenia in patients with a shared ELANE mutation and paternal haplotype: evidence for phenotype determination by modifying genes.
Cyclic neutropenia and severe congenital neutropenia in patients with a shared ELANE mutation and paternal haplotype: evidence for phenotype determination by modifying genes.
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DOI：
10.1002/pbc.22537
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发表时间：
2010-08
影响因子：
3.2
通讯作者：
Boxer, Laurence A.
中科院分区：
文献类型：
--
作者：
Newburger, Peter E.;Pindyck, Talia N.;Zhu, Zhiqing;Bolyard, Audrey Anna;Aprikyan, Andrew A. G.;Dale, David C.;Smith, Gary D.;Boxer, Laurence A.
周期性中性粒细胞减少症（CN）和重度先天性中性粒细胞减少症（SCN）是中性粒细胞产生的疾病，其疾病严重程度明显不同。ELANE基因（最近取代ELA2的符号）的突变被认为是大多数CN和SCN病例的主要原因，但特定的突变通常与其中一种或另一种相关。我们对一个SCN家系的所有个体和父亲精子进行了ELANE基因分型，该家系有8个SCN后代，来自一个精子供体和6个不同的母亲。1例CN患者与7例SCN表型患者具有相同的S97 L ELANE突变。突变等位基因在供体的精子中检测到，占ELANE基因库的18%，但在淋巴细胞、中性粒细胞或颊粘膜的DNA中未检测到，表明性腺嵌合体。CN和SCN表型在该家系中与共享的父系单倍型共存，强烈表明修饰基因在确定先天性中性粒细胞减少症疾病表型中的作用，以及CN和SCN在表达不同程度的相同疾病过程的表型谱内的分类。
Cyclic neutropenia (CN) and severe congenital neutropenia (SCN) are disorders of neutrophil production that differ markedly in disease severity. Mutations of the ELANE gene (the symbol recently replacing ELA2) are considered largely responsible for most cases of CN and SCN, but specific mutations are typically associated with one or the other We performed ELANE genotyping on all individuals and paternal sperm in an SCN kindred with 8 SCN progeny of a sperm donor and 6 different mothers. One patient with CN had the same S97L ELANE mutation as seven patients with the SCN phenotype. The mutant allele was detected in the donor’s spermatozoa, representing 18% of the ELANE gene pool, but not in DNA from his lymphocytes, neutrophils, or buccal mucosa, indicating gonadal mosaicism. The coexistence of CN and SCN phenotypes in this kindred with a shared paternal haplotype strongly suggests both a role for modifying genes in determination of congenital neutropenia disease phenotypes, and the classification of CN and SCN within a spectrum of phenotypes expressing varying degrees of the same disease process.
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影响因子：
9.9
作者：
通讯作者：
--
影响因子：
3.6
作者：
Dale, DC;Bolyard, AA;Aprikyan, A
通讯作者：
Aprikyan, A
影响因子：
6.5
作者：
Rosenberg, Philip S.;Alter, Blanche P.;Dale, David C.
通讯作者：
Dale, David C.
影响因子：
20.3
作者：
Skokowa, Julia;Fobiwe, John Paul;Welte, Karl
通讯作者：
Welte, Karl
影响因子：
158.5
作者：
BONILLA, MA;GILLIO, AP;OREILLY, RJ
通讯作者：
OREILLY, RJ