| 题名 | Somatic mutations and progressive monosomy modify SAMD9-related phenotypes in humans |
| 作者 | Buonocore, Federica1; Kuehnen, Peter2,3; Suntharalingham, Jenifer P.1; Del Valle, Ignacio1; Digweed, Martin4; Stachelscheid, Harald5,6; Khajavi, Noushafarin2,3; Didi, Mohammed7; Brady, Angela F.8; Blankenstein, Oliver2,3; Procter, Annie M.9; Dimitri, Paul10; Wales, Jerry K. H.11; Ghirri, Paolo12; Knoebl, Dieter; Strahm, Brigitte13; Erlacher, Miriam13,14,15; Wlodarski, Marcin W.13,14,15; Chen, Wei16,22,23  ; Kokai, George K.17; Anderson, Glenn18; Morrogh, Deborah19; Moulding, Dale A.20; McKee, Shane A.21; Niemeyer, Charlotte M.13,14,15; Grueters, Annette2,3; Achermann, John C.1
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| 通讯作者 | Achermann, John C. |
| 发表日期 | 2017-05
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| DOI | |
| 发表期刊 | |
| ISSN | 0021-9738
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| EISSN | 1558-8238
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| 卷号 | 127期号:5页码:1700-1713 |
| 摘要 | It is well established that somatic genomic changes can influence phenotypes in cancer, but the role of adaptive changes in developmental disorders is less well understood. Here we have used next-generation sequencing approaches to identify de novo heterozygous mutations in sterile alpha motif domain-containing protein 9 (SAMD9, located on chromosome 7q21.2) in 8 children with a multisystem disorder termed MIRAGE syndrome that is characterized by intrauterine growth restriction (IUGR) with gonadal, adrenal, and bone marrow failure, predisposition to infections, and high mortality. These mutations result in gain of function of the growth repressor product SAMD9. Progressive loss of mutated SAMD9 through the development of monosomy 7 (-7), deletions of 7q (7q-), and secondary somatic loss-of-function (nonsense and frameshift) mutations in SAMD9 rescued the growth-restricting effects of mutant SAMD9 proteins in bone marrow and was associated with increased length of survival. However, 2 patients with -7 and 7q-developed myelodysplastic syndrome, most likely due to haploinsufficiency of related 7q21.2 genes. Taken together, these findings provide strong evidence that progressive somatic changes can occur in specific tissues and can subsequently modify disease phenotype and influence survival. Such tissue-specific adaptability may be a more common mechanism modifying the expression of human genetic conditions than is currently recognized. |
| 相关链接 | [来源记录] |
| 收录类别 | |
| 语种 | 英语
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| 重要成果 | NI论文
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| 学校署名 | 其他
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| 资助项目 | German Research Foundation (DFG)[KU2673/2-1]
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| WOS研究方向 | Research & Experimental Medicine
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| WOS类目 | Medicine, Research & Experimental
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| WOS记录号 | WOS:000400381000015
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| 出版者 | |
| ESI学科分类 | CLINICAL MEDICINE
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| 来源库 | Web of Science
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| 引用统计 |
被引频次[WOS]：120
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| 成果类型 | 期刊论文 |
| 条目标识符 | http://sustech.caswiz.com/handle/2SGJ60CL/28976 |
| 专题 | 生命科学学院_生物系 前沿与交叉科学研究院 |
| 作者单位 | 1.UCL, Genet & Genom Med, Great Ormond St Inst Child Hlth, 30 Guilford St, London WC1N 1EH, England 2.Charite, Inst Expt Pediat Endocrinol, Berlin, Germany 3.Charite, Dept Pediat Endocrinol, Berlin, Germany 4.Charite, Dept Human & Med Genet, Berlin, Germany 5.Berlin Inst Hlth, Berlin, Germany 6.Charite, Berlin Brandenburg Ctr Regenerat Therapies, Berlin, Germany 7.Alder Hey Childrens NHS Fdn Trust, Dept Paediat Endocrinol, Liverpool, Merseyside, England 8.Northwick Pk Hosp & Clin Res Ctr, North West Thames Reg Genet Serv, Harrow, Middx, England 9.Univ Wales Hosp, Inst Med Genet, Cardiff, S Glam, Wales 10.Univ Sheffield, Acad Unit Child Hlth, Sheffield, S Yorkshire, England 11.Univ Queensland, Dept Endocrinol, Childrens Hlth Queensland Clin Unit, Brisbane, Qld, Australia 12.Univ Pisa, Dept Neonatol, Pisa, Italy 13.Univ Freiburg, Fac Med, Med Ctr Univ Freiburg, Dept Pediat & Adolescent Med,Div Pediat Hematol &, Freiburg, Germany 14.German Canc Consortium DKTK, Heidelberg, Germany 15.German Res Ctr DKFZ, Heidelberg, Germany 16.Max Delbruck Ctr Mol Med, Berlin, Germany 17.Alder Hey Childrens NHS Fdn Trust, Dept Paediat Histopathol, Liverpool, Merseyside, England 18.Great Ormond St Hosp Children NHS Fdn Trust, Histopathol Dept, London, England 19.Great Ormond St Hosp Children NHS Fdn Trust, North East Thames Reg Genet Lab Serv, London, England 20.UCL, Great Ormond St Inst Child Hlth, Dev Biol & Canc, London, England 21.Belfast City Hosp, Dept Med Genet, Belfast, Antrim, North Ireland 22.Southern Univ Sci & Technol, Dept Biol, Shenzhen, Guangdong, Peoples R China 23.Southern Univ Sci & Technol, Medi X Inst, SUSTech Acad Adv Interdisciplinary Studies, Shenzhen, Guangdong, Peoples R China |
| 推荐引用方式 GB/T 7714 |
Buonocore, Federica,Kuehnen, Peter,Suntharalingham, Jenifer P.,et al. Somatic mutations and progressive monosomy modify SAMD9-related phenotypes in humans[J]. JOURNAL OF CLINICAL INVESTIGATION,2017,127(5):1700-1713.
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| APA |
Buonocore, Federica.,Kuehnen, Peter.,Suntharalingham, Jenifer P..,Del Valle, Ignacio.,Digweed, Martin.,...&Achermann, John C..(2017).Somatic mutations and progressive monosomy modify SAMD9-related phenotypes in humans.JOURNAL OF CLINICAL INVESTIGATION,127(5),1700-1713.
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| MLA |
Buonocore, Federica,et al."Somatic mutations and progressive monosomy modify SAMD9-related phenotypes in humans".JOURNAL OF CLINICAL INVESTIGATION 127.5(2017):1700-1713.
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| 条目包含的文件 | ||||||
| 文件名称/大小 | 文献类型 | 版本类型 | 开放类型 | 使用许可 | 操作 | |
| buonocore2017.pdf（2486KB） | -- | -- | 限制开放 | -- | ||
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