Mutations in GATA2 cause primary lymphedema associated with a predisposition to acute myeloid leukemia (Emberger syndrome)

被引：399

作者：

Ostergaard, Pia ^{[2
]}

Simpson, Michael A. ^{[3
]}

Connell, Fiona C. ^{[4
]}

Steward, Colin G. ^{[5
]}

Brice, Glen ^{[1
]}

Woollard, Wesley J. ^{[3
]}

Dafou, Dimitra ^{[3
]}

Kilo, Tatjana ^{[6
]}

Smithson, Sarah ^{[7
]}

Lunt, Peter ^{[7
]}

Murday, Victoria A. ^{[8
]}

Hodgson, Shirley ^{[1
]}

Keenan, Russell ^{[9
]}

Pilz, Daniela T. ^{[10
]}

Martinez-Corral, Ines ^{[11
]}

Makinen, Taija ^{[11
]}

Mortimer, Peter S. ^{[12
]}

Jeffery, Steve ^{[2
]}

Trembath, Richard C. ^{[3
]}

Mansour, Sahar ^{[1
]}

机构：

[1] St Georges Univ London, SW Thames Reg Genet Serv, London, England

[2] St Georges Univ London, Med Genet Unit, London, England

[3] Kings Coll London, Sch Med, Div Genet & Mol Med, Guys Hosp, London WC2R 2LS, England

[4] Guys Hosp, Guys & St Thomas Natl Hlth Serv NHS Fdn Trust, London SE1 9RT, England

[5] Royal Hosp Children, Bone Marrow Transplant Unit, Bristol, Avon, England

[6] Childrens Hosp Westmead, Haematol Unit, Sydney, NSW, Australia

[7] St Michaels Hosp, Dept Clin Genet, Bristol, Avon, England

[8] Yorkhill Hosp, Dept Clin Genet, Glasgow, Lanark, Scotland

[9] Alder Hey Childrens Hosp, Dept Paediat Haematol, Liverpool L12 2AP, Merseyside, England

[10] Univ Wales Hosp, Inst Med Genet, Cardiff CF4 4XN, S Glam, Wales

[11] Canc Res UK London Res Inst, Lymphat Dev Lab, London, England

[12] St Georges Univ London, Dept Cardiac & Vasc Sci, London, England

来源：

NATURE GENETICS | 2011年 / 43卷 / 10期

关键词：

MYELODYSPLASIA; CEBPA;

D O I：

10.1038/ng.923

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

We report an allelic series of eight mutations in GATA2 underlying Emberger syndrome, an autosomal dominant primary lymphedema associated with a predisposition to acute myeloid leukemia. GATA2 is a transcription factor that plays an essential role in gene regulation during vascular development and hematopoietic differentiation. Our findings indicate that haploinsufficiency of GATA2 underlies primary lymphedema and predisposes to acute myeloid leukemia in this syndrome.

引用

页码：929 / 931

页数：3

共 15 条

[1]

Detection of an Interstitial 3q21.1-q21.3 Deletion in a Child With Multiple Congenital Abnormalities, Mental Retardation, Pancytopenia, and Myelodysplasia [J].

Callier, P. ;

Faivre, L. ;

Marle, N. ;

Thauvin-Robinet, C. ;

Guy, J. ;

Mosca, A. L. ;

D'Athis, P. ;

Masurel-Paulet, A. ;

Assous, D. ;

Teyssier, J. R. ;

Huet, F. ;

Mugneret, F. .

AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 2009, 149A (06) :1323-1326

[2]

DICKINSON RE, 2011, BLOOD 0715, DOI DOI 10.1182/BLOOD-2011-06-360313

[3]

Gata2 Is Required for the Development of Inner Ear Semicircular Ducts and the Surrounding Perilymphatic Space [J].

Haugas, Maarja ;

Lillevali, Kersti ;

Hakanen, Janne ;

Salminen, Marjo .

DEVELOPMENTAL DYNAMICS, 2010, 239 (09) :2452-2469

[4]

HSU AP, 2011, BLOOD 0613, DOI DOI 10.1182/BLOOD-2011-05-356352

[5]

A Gata2 intronic enhancer confers its pan-endothelia-specific regulation [J].

Khandekar, Melin ;

Brandt, William ;

Zhou, Yinghui ;

Dagenais, Susan ;

Glover, Thomas W. ;

Suzuki, Norio ;

Shimizu, Ritsuko ;

Yamamoto, Masayuki ;

Lim, Kim-Chew ;

Engel, James Douglas .

DEVELOPMENT, 2007, 134 (09) :1703-1712

[6]

Emberger Syndrome-Primary Lymphedema With Myelodysplasia: Report of Seven New Cases [J].

Mansour, Sahar ;

Connell, Fiona ;

Steward, Colin ;

Ostergaard, Pia ;

Brice, Glen ;

Smithson, Sarah ;

Lunt, Peter ;

Jeffery, Steve ;

Dokal, Inderjeet ;

Vulliamy, Tom ;

Gibson, Brenda ;

Hodgson, Shirley ;

Cottrell, Sally ;

Kiely, Louise ;

Tinworth, Lorna ;

Kalidas, Kamini ;

Mufti, Ghulam ;

Cornish, Jackie ;

Keenan, Russell ;

Mortimer, Peter ;

Murday, Victoria .

AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 2010, 152A (09) :2287-2296

[7]

Dominant-negative mutations of CEBPA, encoding CCAAT/enhancer binding protein-α (C/EBPα), in acute myeloid leukemia [J].

Pabst, T ;

Mueller, BU ;

Zhang, P ;

Radomska, HS ;

Narravula, S ;

Schnittger, S ;

Behre, G ;

Hiddemann, W ;

Tenen, DG .

NATURE GENETICS, 2001, 27 (03) :263-270

[8]

High incidence of biallelic point mutations in the Runt domain of the AML1/PEBP2αB gene in Mo acute myeloid leukemia and in myeloid malignancies with acquired trisomy 21 [J].

Preudhomme, C ;

Warot-Loze, D ;

Roumier, C ;

Grardel-Duflos, N ;

Garand, R ;

Lai, JL ;

Dastugue, N ;

Macintyre, E ;

Denis, C ;

Bauters, F ;

Kerckaert, JP ;

Cosson, A ;

Fenaux, P .

BLOOD, 2000, 96 (08) :2862-2869

[9]

GATA-2 regulates granulocyte-macrophage progenitor cell function [J].

Rodrigues, Neil P. ;

Boyd, Ashleigh S. ;

Fugazza, Cristina ;

May, Gillian E. ;

Guo, YanPing ;

Tipping, Alex J. ;

Scadden, David T. ;

Vyas, Paresh ;

Enver, Tariq .

BLOOD, 2008, 112 (13) :4862-4873

[10]

Brief report - Mutation of CEBPA in familial acute myeloid leukemia [J].

Smith, ML ;

Cavenagh, JD ;

Lister, TA ;

Fitzgibbon, J .

NEW ENGLAND JOURNAL OF MEDICINE, 2004, 351 (23) :2403-2407

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