Prevalence of mutations in ELANE, GFI1, HAX1, SBDS, WAS and G6PC3 in patients with severe congenital neutropenia.
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.
Division of Oncology, Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA.
Jun
J
Xia
Audrey A
AA
Bolyard
Elin
E
Rodger
Steve
S
Stein
Andrew A
AA
Aprikyan
David C
DC
Dale
Daniel C
DC
Link
D048868:Adaptor Proteins, Signal Transducing; D002908:Chronic Disease; D004252:DNA Mutational Analysis / Q000379:methods; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005952:Glucose-6-Phosphatase / Q000235:genetics; D006801:Humans; D019272:Leukocyte Elastase / Q000235:genetics*; D008297:Male; D009154:Mutation; D009503:Neutropenia / Q000151:congenital / Q000235:genetics*; D011506:Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D051316:Wiskott-Aldrich Syndrome Protein / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C498275:GFI1 protein, human; C104759:HAX1 protein, human; D011506:Proteins; C470521:SBDS protein, human; D014157:Transcription Factors; C495767:WAS protein, human; D051316:Wiskott-Aldrich Syndrome Protein; D005952:Glucose-6-Phosphatase; C492193:G6PC3 protein, human; D019272:Leukocyte Elastase