Prevalence of mutations in ELANE, GFI1, HAX1, SBDS, WAS and G6PC3 in patients with severe congenital neutropenia.
Prevalence of mutations in ELANE, GFI1, HAX1, SBDS, WAS and G6PC3 in patients with severe congenital neutropenia.
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DOI：
10.1111/j.1365-2141.2009.07888.x
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发表时间：
2009-11
影响因子：
6.5
通讯作者：
Link DC
中科院分区：
文献类型：
--
作者：
Xia J;Bolyard AA;Rodger E;Stein S;Aprikyan AA;Dale DC;Link DC
严重先天性中性粒细胞减少症 (SCN) 是一种与 ELANE (ELA2)、HAX1、GFI1、WAS、CSF3R 或 G6PC3 突变相关的遗传异质性综合征。我们调查了 162 名 SCN 患者的 ELANE 突变患病率，这些患者的血液或骨髓样本已提交给北美严重慢性中性粒细胞减少症组织存储库。 162 名患者中有 90 名（55.6%）发现 ELANE 突变。随后，我们利用高通量测序方法对其中 73 个病例的子集进行了分析，以确定与 SCN 相关的其他突变的患病率。 73例患者中，28例检测到ELANE突变。其余45例携带野生型ELANE等位基因的患者中，5例患者出现突变：GFI1（1）、SBDS（1）、WAS（1）和G6PC3（2）；未检测到HAX1突变。在大约 40% 的病例中，SCN 的遗传基础仍然未知。这些数据表明，对于SCN的基因诊断，应首先进行ELANE基因分型。在没有ELANE突变的患者中，很少会发现其他已知的SCN相关基因突变，并且可以根据每个患者的临床特征来指导基因分型。
Severe congenital neutropenia (SCN) is a genetically heterogeneous syndrome associated with mutations of ELANE (ELA2), HAX1, GFI1, WAS, CSF3R or G6PC3. We investigated the prevalence of mutations of ELANE in a cohort of 162 SCN patients for whom blood or bone marrow samples were submitted to the North American Severe Chronic Neutropenia Tissue Repository. Mutations of ELANE were found in 90 of 162 patients (55.6%). Subsequently, we conducted an analysis of a subset of 73 of these cases utilizing a high throughput sequencing approach to determine the prevalence of other mutations associated with SCN. Among the 73 patients, mutations of ELANE were detected in 28. In the remaining 45 patients with wild type ELANE alleles, 5 patients had mutations: GFI1 (1), SBDS (1), WAS (1) and G6PC3 (2); no mutations of HAX1 were detected. In approximately 40% of our cases, the genetic basis of SCN remains unknown. These data suggest that for genetic diagnosis of SCN, ELANE genotyping should first be performed. In patients without ELANE mutations, other known SCN-associated gene mutations will be found rarely and genotyping can be guided by the clinical features of each patient.
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影响因子：
6.5
作者：
Germeshausen, M;Schulze, H;Welte, K
通讯作者：
Welte, K
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：
Germeshausen, Manuela;Grudzien, Magda;Klein, Christoph
通讯作者：
Klein, Christoph
影响因子：
11.1
作者：
Carlsson, G.;van't Hooft, I.;Henter, J-I
通讯作者：
Henter, J-I
影响因子：
4
作者：
Ishikawa, N.;Okada, S.;Kobayashi, M.
通讯作者：
Kobayashi, M.