Systematic molecular genetic analysis of congenital sideroblastic anemia: evidence for genetic heterogeneity and identification of novel mutations.
Systematic molecular genetic analysis of congenital sideroblastic anemia: evidence for genetic heterogeneity and identification of novel mutations.
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先天性铁粒幼细胞贫血的系统分子遗传学分析：遗传异质性的证据和新突变的鉴定。
DOI：
10.1002/pbc.22244
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发表时间：
2010-02
影响因子：
3.2
通讯作者：
Neufeld, Ellis J.
中科院分区：
文献类型：
--
作者：
Bergmann, Anke K.;Campagna, Dean R.;McLoughlin, Erin M.;Agarwal, Suneet;Fleming, Mark D.;Bottomley, Sylvia S.;Neufeld, Ellis J.
铁粒幼细胞性贫血是异质性先天性和后天性骨髓疾病，其特征是红细胞前体线粒体中病理性铁沉积。在先天性铁粒幼细胞贫血 (CSA) 中，最常见的形式是 X 连锁铁粒幼细胞贫血，由 5-氨基乙酰丙酸合酶 (ALAS2) 突变所致。最近定义了一种由红系特异性线粒体转运蛋白 SLC25A38 突变引起的新型常染色体隐性 CSA。其他已知的病因包括编码硫胺素转运蛋白 (SLC19A2)、RNA 修饰酶假尿苷合酶 1 (PUS1)、线粒体 ATP 结合盒转运蛋白 (ABCB7)、谷氧还蛋白 5 (GLRX5) 的基因突变以及线粒体 DNA 缺失。尽管存在这些已知的多种原因，但在大部分 CSA 病例中，推测的遗传缺陷仍然未知。在最近发现 SLC25A38 作为一个主要新病因的背景下，我们系统地分析了一大群以前未报告的 CSA 患者。对 60 名 CSA 先证者（28 名女性，32 名男性）进行了 ALAS2、SLC25A38、PUS1、GLRX5 和 ABCB7 突变检查。仅在症状特征明显时才分析 SLC19A2 和线粒体 DNA。 12 名先证者的 SLC25A38 具有双等位基因突变。在 8 例散发性 CSA 病例中检测到 7 种 ALAS2 突变，其中 2 例为新突变。我们还在两名皮尔逊综合征患者中发现了一种新的纯合性 PUS1 无效突变和新的线粒体 DNA 缺失。 GLRX5、ABCB7 或 SLC19A2 中未遇到突变。其余未定义的先证者 (43%) 可根据性别、家庭和临床特征进行分组，表明 CSA 存在新的 X 连锁和常染色体隐性遗传形式。
Sideroblastic anemias are heterogeneous congenital and acquired bone marrow disorders characterized by pathologic iron deposits in mitochondria of erythroid precursors. Among the congenital sideroblastic anemias (CSAs), the most common form is X-linked sideroblastic anemia, due to mutations in 5-aminolevulinate synthase (ALAS2). A novel autosomal recessive CSA, caused by mutations in the erythroid specific mitochondrial transporter SLC25A38, was recently defined. Other known etiologies include mutations in genes encoding the thiamine transporter (SLC19A2), the RNA-modifying enzyme pseudouridine synthase 1 (PUS1), a mitochondrial ATP-binding cassette transporter (ABCB7), glutaredoxin 5 (GLRX5), as well as mitochondrial DNA deletions. Despite these known diverse causes, in a substantial portion of CSA cases a presumed genetic defect remains unknown. In the context of the recent discovery of SLC25A38 as a major novel cause, we systematically analyzed a large cohort of previously unreported CSA patients. Sixty CSA probands (28 females, 32 males) were examined for ALAS2, SLC25A38, PUS1, GLRX5, and ABCB7 mutations. SLC19A2 and mitochondrial DNA were only analyzed if characteristic syndromic features were apparent. Twelve probands had biallelic mutations in SLC25A38. Seven ALAS2 mutations were detected in eight sporadic CSA cases, two being novel. We also identified a novel homozygous null PUS1 mutation and novel mitochondrial DNA deletions in two patients with Pearson syndrome. No mutationswere encountered in GLRX5, ABCB7, or SLC19A2. The remaining undefined probands (43%) can be grouped according to gender, family and clinical characteristics, suggesting novel X-linked and autosomal recessive forms of CSA.
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影响因子：
5.1
作者：
ABBOUD, MR;ALEXANDER, D;NAJJAR, SS
通讯作者：
NAJJAR, SS
影响因子：
9.8
作者：
Bykhovskaya, Y;Casas, K;Fischel-Ghodsian, N
通讯作者：
Fischel-Ghodsian, N
影响因子：
11.4
作者：
Astner, I;Schulze, JO;Heinz, DW
通讯作者：
Heinz, DW
影响因子：
2.3
作者：
Neufeld, EJ;Fleming, JC;Steinkamp, MP
通讯作者：
Steinkamp, MP
影响因子：
4
作者：
Fernandez-Vizarra, Erika;Berardinelli, Angela;Zeviani, Massimo
通讯作者：
Zeviani, Massimo