Prevalence of mutations in ELANE, GFI1, HAX1, SBDS, WAS and G6PC3 in patients with severe congenital neutropenia

被引:129
作者
Xia, Jun [2 ]
Bolyard, Audrey A. [1 ]
Rodger, Elin [1 ]
Stein, Steve [1 ]
Aprikyan, Andrew A. [1 ]
Dale, David C. [1 ]
Link, Daniel C. [2 ]
机构
[1] Univ Washington, Dept Med, Seattle, WA 98195 USA
[2] Washington Univ, Sch Med, Dept Med, Div Oncol, St Louis, MO 63110 USA
基金
美国国家卫生研究院;
关键词
bone marrow failure; chronic neutropenia; DNA mutation; G-CSF; ELASTASE; PHENOTYPE;
D O I
10.1111/j.1365-2141.2009.07888.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 utilising 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, five 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.
引用
收藏
页码:535 / 542
页数:8
相关论文
共 26 条
[1]   Two novel activating mutations in the Wiskott-Aldrich syndrome protein result in congenital neutropenia [J].
Ancliff, Phil J. ;
Blundell, Michael P. ;
Cory, Giles O. ;
Calle, Yolanda ;
Worth, Austen ;
Kempski, Helena ;
Burns, Siobhan ;
Jones, Gareth E. ;
Sinclair, Jo ;
Kinnon, Christine ;
Hann, Ian M. ;
Gale, Rosemary E. ;
Linch, David C. ;
Thrasher, Adrian J. .
BLOOD, 2006, 108 (07) :2182-2189
[2]   Paternal mosaicism proves the pathogenic nature of mutations in neutrophil elastase in severe congenital neutropenia [J].
Ancliff, PJ ;
Gale, RE ;
Watts, MJ ;
Liesner, R ;
Hann, IM ;
Strobel, S ;
Linch, DC .
BLOOD, 2002, 100 (02) :707-709
[3]   Mutations in the ELA2 gene encoding neutrophil elastase are present in most patients with sporadic severe congenital neutropenia but only in some patients with the familial form of the disease [J].
Ancliff, PJ ;
Gale, RE ;
Liesner, R ;
Hann, IM ;
Linch, DC .
BLOOD, 2001, 98 (09) :2645-2650
[4]   Mutations in the ELA2 gene correlate with more severe expression of neutropenia:: a study of 81 patients from the French Neutropenia Register [J].
Bellanné-Chantelot, C ;
Clauin, S ;
Leblanc, T ;
Cassinat, B ;
Rodrigues-Lima, F ;
Beaufils, S ;
Vaury, C ;
Barkaoui, M ;
Fenneteau, O ;
Maier-Redelsperger, M ;
Chomienne, C ;
Donadieu, J .
BLOOD, 2004, 103 (11) :4119-4125
[5]   Mutations in SBDS are associated with Shwachman-Diamond syndrome [J].
Boocock, GRB ;
Morrison, JA ;
Popovic, M ;
Richards, N ;
Ellis, L ;
Durie, PR ;
Rommens, JM .
NATURE GENETICS, 2003, 33 (01) :97-101
[6]   A Syndrome with Congenital Neutropenia and Mutations in G6PC3 [J].
Boztug, Kaan ;
Appaswamy, Giridharan ;
Ashikov, Angel ;
Schaffer, Alejandro A. ;
Salzer, Ulrich ;
Diestelhorst, Jana ;
Germeshausen, Manuela ;
Brandes, Gudrun ;
Lee-Gossler, Jacqueline ;
Noyan, Fatih ;
Gatzke, Anna-Katherina ;
Minkov, Milen ;
Greil, Johann ;
Kratz, Christian ;
Petropoulou, Theoni ;
Pellier, Isabelle ;
Bellanne-Chantelot, Christine ;
Rezaei, Nima ;
Moenkemoeller, Kirsten ;
Irani-Hakimeh, Noha ;
Bakker, Hans ;
Gerardy-Schahn, Rita ;
Zeidler, Cornelia ;
Grimbacher, Bodo ;
Welte, Karl ;
Klein, Christoph .
NEW ENGLAND JOURNAL OF MEDICINE, 2009, 360 (01) :32-43
[7]   Mutations in the SBDS gene in acquired aplastic anemia [J].
Calado, Rodrigo T. ;
Graf, Solomon A. ;
Wilkerson, Keisha L. ;
Kajigaya, Sachiko ;
Ancliff, Philip J. ;
Dror, Yigal ;
Chanock, Stephen J. ;
Lansdorp, Peter M. ;
Young, Neal S. .
BLOOD, 2007, 110 (04) :1141-1146
[8]   Central nervous system involvement in severe congenital neutropenia:: neurological and neuropsychological abnormalities associated with specific HAX1 mutations [J].
Carlsson, G. ;
van't Hooft, I. ;
Melin, M. ;
Entesarian, M. ;
Laurencikas, E. ;
Nennesmo, I. ;
Trebinska, A. ;
Grzybowska, E. ;
Palmblad, J. ;
Dahl, N. ;
Nordenskjold, M. ;
Fadeel, B. ;
Henter, J-I .
JOURNAL OF INTERNAL MEDICINE, 2008, 264 (04) :388-400
[9]  
Carlsson G, 2006, HAEMATOLOGICA, V91, P589
[10]   Mutations in the gene encoding neutrophil elastase in congenital and cyclic neutropenia [J].
Dale, DC ;
Person, RE ;
Bolyard, AA ;
Aprikyan, AG ;
Bos, C ;
Bonilla, MA ;
Boxer, LA ;
Kannourakis, G ;
Zeidler, C ;
Welte, K ;
Benson, KF ;
Horwitz, M .
BLOOD, 2000, 96 (07) :2317-2322