Extended Spectrum of Human Glucose-6-Phosphatase Catalytic Subunit 3 Deficiency: Novel Genotypes and Phenotypic Variability in Severe Congenital Neutropenia

被引：53

作者：

Boztug, Kaan ^{[1
,2
,3
]}

Rosenberg, Philip S. ^{[5
]}

Dorda, Marie ^{[3
]}

Banka, Siddharth ^{[7
]}

Moulton, Thomas ^{[8
]}

Curtin, Julie ^{[9
]}

Rezaei, Nima ^{[10
,11
,12
]}

Corns, John ^{[14
]}

Innis, Jeffrey W. ^{[15
]}

Avci, Zekai ^{[17
]}

Hung Chi Tran ^{[18
]}

Pellier, Isabelle ^{[19
]}

Pierani, Paolo ^{[20
]}

Fruge, Rachel ^{[21
]}

Parvaneh, Nima ^{[12
]}

Mamishi, Setareh ^{[13
]}

Mody, Rajen ^{[16
]}

Darbyshire, Phil ^{[23
]}

Motwani, Jayashree ^{[23
]}

Murray, Jennie ^{[24
]}

Buchanan, George R. ^{[22
]}

Newman, William G. ^{[7
]}

Alter, Blanche P. ^{[6
]}

Boxer, Laurence A. ^{[16
]}

Donadieu, Jean ^{[25
]}

Welte, Karl ^{[4
]}

Klein, Christoph ^{[3
,26
]}

机构：

[1] Austrian Acad Sci CeMM, Res Ctr Mol Med, A-1090 Vienna, Austria

[2] Med Univ Vienna, Dept Pediat & Adolescent Med, Vienna, Austria

[3] Hannover Med Sch, Dept Pediat Hematol Oncol, D-3000 Hannover, Germany

[4] Hannover Med Sch, Dept Mol Hematopoiesis, D-3000 Hannover, Germany

[5] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD USA

[6] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD USA

[7] St Marys Hosp, Manchester Acad Hlth Sci Ctr, Manchester M13 0JH, Lancs, England

[8] Bronx Lebanon Hosp Ctr, Dept Pediat Hematol Oncol, Bronx, NY USA

[9] Childrens Hosp Westmead, Dept Hematol, Sydney, NSW, Australia

[10] Univ Tehran Med Sci, Mol Immunol Res Ctr, Tehran, Iran

[11] Univ Tehran Med Sci, Dept Immunol, Sch Med, Tehran, Iran

[12] Univ Tehran Med Sci, Childrens Med Ctr, Res Ctr Immunodeficiencies, Tehran, Iran

[13] Univ Tehran Med Sci, Infect Dis Res Ctr, Tehran, Iran

[14] Nationwide Childrens Hosp, Dept Pediat Hematol Oncol, Columbus, OH USA

[15] Univ Michigan, Div Pediat Genet, Ann Arbor, MI 48109 USA

[16] Univ Michigan Hosp, Dept Pediat, Ann Arbor, MI 48109 USA

[17] Kecioren Res & Training Hosp, Dept Pediat Hematol, Ankara, Turkey

[18] Childrens Hosp Los Angeles, Dept Pediat, Div Hematol Oncol, Los Angeles, CA 90027 USA

[19] CHU Angers, Angers, France

[20] Polytech Univ Marche, G Salesi Womens & Childrens Hosp, Inst Mother & Child Hlth, Div Pediat Hematol Oncol, Ancona, Italy

[21] Childrens Med Ctr, Ctr Canc & Blood Disorders, Dallas, TX 75235 USA

[22] Univ Texas SW Med Ctr Dallas, Dept Pediat, Div Hematol Oncol, Dallas, TX 75390 USA

[23] Birmingham Childrens Hosp, Dept Haematol, Birmingham, W Midlands, England

[24] Western Gen Hosp, SE Scotland Clin Genet Serv, Edinburgh EH4 2XU, Midlothian, Scotland

[25] Hop Trousseau, Serv Hemato Oncol Pediat, F-75571 Paris, France

[26] Univ Munich, Univ Childrens Hosp, Munich, Germany

来源：

JOURNAL OF PEDIATRICS | 2012年 / 160卷 / 04期

基金：

美国国家卫生研究院;

关键词：

STEM-CELL TRANSPLANTATION; MUTATIONS; LEUKEMIA; G6PC3; EXPERIENCE; MORTALITY; ELASTASE; RISK; HAX1; GFI1;

D O I：

10.1016/j.jpeds.2011.09.019

中图分类号：

R72 [儿科学];

学科分类号：

100202 ;

摘要：

Objective To delineate the phenotypic and molecular spectrum of patients with a syndromic variant of severe congenital neutropenia (SCN) due to mutations in the gene encoding glucose-6-phosphatase catalytic subunit 3 (G6PC3). Study design Patients with syndromic SCN were characterized for associated malformations and referred to us for G6PC3 mutational analysis. Results In a cohort of 31 patients with syndromic SCN, we identified 16 patients with G6PC3 deficiency including 11 patients with novel biallelic mutations. We show that nonhematologic features of G6PC3 deficiency are good predictive indicators for mutations in G6PC3. Additionally, we demonstrate genetic variability in this disease and define novel features such as growth hormone deficiency, genital malformations, disrupted bone remodeling, and abnormalities of the integument. G6PC3 mutations may be associated with hydronephrosis or facial dysmorphism. The risk of transition to myelodysplastic syndrome/acute myeloid leukemia may be lower than in other genetically defined SCN subgroups. Conclusions The phenotypic and molecular spectrum in G6PC3 deficiency is wider than previously appreciated. The risk of transition to myelodysplastic syndrome or acute myeloid leukemia may be lower in G6PC3 deficiency compared with other subgroups of SCN. (J Pediatr 2012;160:679-83).

引用

页码：679 / +

页数：7

共 34 条

[21] SIMPLE EXACT ANALYSIS OF THE STANDARDIZED MORTALITY RATIO [J].