Mutational spectrum in congenital dyserythropoietic anemia type II: identification of 19 novel variants in SEC23B gene.
Mutational spectrum in congenital dyserythropoietic anemia type II: identification of 19 novel variants in SEC23B gene.
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DOI：
10.1002/ajh.21866
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发表时间：
2010-12
影响因子：
12.8
通讯作者：
Iolascon, Achille
中科院分区：
文献类型：
--
作者：
Russo, Roberta;Esposito, Maria Rosaria;Asci, Roberta;Gambale, Antonella;Perrotta, Silverio;Ramenghi, Ugo;Forni, Gian Luca;Uygun, Vedat;Delaunay, Jean;Iolascon, Achille
SEC 23 B基因编码外壳蛋白复合物II（COPII）包被囊泡的重要组成部分。该基因的突变导致绝大多数先天性红细胞生成不良性贫血II型（CDA II），这是一种罕见的红细胞生成受损引起的疾病。在这里，我们调查了28名CDA II患者从21个无关的家庭在CDA II国际注册。总的来说，我们发现了19个新的变异体[c.2270 A>C p.H757 P; c.2149−2 A>G; c.1109+1 G>A; c.387（delG）p.L129LfsX26; c.1858 A>G p.M620 V; c.1832 G>C p.R611 P; c.1735 T>A p.Y579 N; c.1254 T>G p.I418 M; c.1015 C>T p.R339 X; c.1254 T>G p.I418 M; c.1015 C>T p.R339 X; C.1603 C>T p.R535X; c.1654 C>T p.L552F; c.1307 C>T p.S436L; c.279+3 A>G; c. 2150（delC）p.A717VfsX7; c.1733 T>C p.L578P; c.1109+5 G>A; c.221+31 A>G; c.367 C>T p.R123X; c.1857_1859delCAT; p.I619del]，呈纯合或复合杂合状态。未发现两个无义突变的纯合性或复合杂合性，有4例测序分析未发现两个突变。为了讨论错义突变的推定功能后果，进行了计算分析和序列比对。我们的数据强调了CDA II的高度等位基因异质性，因为大多数SEC 23 B变异都是作为私人突变遗传的。在这次突变更新中，我们还提供了一种工具，通过定义每个外显子中的突变频率来改善和促进CDA II的分子诊断。Am.血液学杂志，2010.© 2010 Wiley-Liss公司。
SEC23B gene encodes an essential component of the coat protein complex II (COPII)-coated vesicles. Mutations in this gene cause the vast majority the congenital dyserythropoietic anemia Type II (CDA II), a rare disorder resulting from impaired erythropoiesis. Here, we investigated 28 CDA II patients from 21 unrelated families enrolled in the CDA II International Registry. Overall, we found 19 novel variants [c.2270 A>C p.H757P; c.2149−2 A>G; c.1109+1 G>A; c.387(delG) p.L129LfsX26; c.1858 A>G p.M620V; c.1832 G>C p.R611P; c.1735 T>A p.Y579N; c.1254 T>G p.I418M; c.1015 C>T p.R339X; c.1603 C>T p.R535X; c.1654 C>T p.L552F; c.1307 C>T p.S436L; c.279+3 A>G; c. 2150(delC) p.A717VfsX7; c.1733 T>C p.L578P; c.1109+5 G>A; c.221+31 A>G; c.367 C>T p.R123X; c.1857_1859delCAT; p.I619del] in the homozygous or the compound heterozygous state. Homozygosity or compound heterozygosity for two nonsense mutations was never found. In four cases the sequencing analysis has failed to find two mutations. To discuss the putative functional consequences of missense mutations, computational analysis and sequence alignment were performed. Our data underscore the high allelic heterogeneity of CDA II, as the most of SEC23B variations are inherited as private mutations. In this mutation update, we also provided a tool to improve and facilitate the molecular diagnosis of CDA II by defining the frequency of mutations in each exon. Am. J. Hematol., 2010. © 2010 Wiley-Liss, Inc.
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