De novo mutations of \(\textit{ ELANE}\) gene in three Vietnamese patients with severe congenital neutropenia


  • Duong Anh Linh Institute of Genome Research, VAST, Vietnam
  • Nguyen Thi Van Anh Immunology and Rheumatology and Rheumatology Department, Vietnam National Hospital Pediatrics, Vietnam
  • Nguyen Van Tung Institute of Genome Research, VAST, Vietnam
  • Nguyen Huy Hoang Institute of Genome Research, VAST, Vietnam
  • Ngo Diem Ngoc Human Genetics Department, Vietnam National Hospital of Pediatrics, Vietnam
  • Nguyen Thi Phuong Mai Human Genetics Department, Vietnam National Hospital of Pediatrics, Vietnam
  • Ngo Manh Tien Human Genetics Department, Vietnam National Hospital of Pediatrics, Vietnam
  • Nguyen Thi Kim Lien Institute of Genome Research, VAST, Vietnam



De novo, ELANE, severe congenital neutropenia, Vietnamese, whole-exome sequencing


Severe congenital neutropenia (SCN) is a congenital condition in which granulocytes mature abnormally owing to a variety of genetic defects, resulting in immunodeficiency. Among the several genetic variations related to SCN, heterozygous mutations in the ELANE gene encoding neutrophil elastase account for approximately 60% of the genetic causes. Here, we present three patients from different Vietnamese families who were susceptible to infectious diseases such as lung abscesses, sepsis, cellulitis, and septicemia. Moreover, their hematological and immunological parameters were below the reference range. Whole exome sequencing (WES) analysis was performed in all cases harboring three previously described disease-causing mutations, including p.Arg103Pro, p.Trp156Arg, and p.Arg81Pro in the ELANE gene (NM_001972.4). These mutations were confirmed by the Sanger sequencing method in the patients, helping to identify de novo mutations in all cases. Our data increase more evidence for the function of ELANE in SCN, as well as raise awareness of this rare disease in the context of frequent infections in Vietnam.


Download data is not yet available.


Metrics Loading ...


Bellanne-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., 2004. Mutations in the ELA2 gene correlate with more severe expression of neutropenia: a study of 81 patients from the French Neutropenia Register. Blood, 103(11): 4119-4125.

Calyseva J., Vihinen M., 2017. PON-SC - program for identifying steric clashes caused by amino acid substitutions. BMC Bioinformatics, 18(1): 531.

Dale D.C., Person R.E., Bolyard A.A., Aprikyan A.G., Bos C., Bonilla M.A., Boxer L.A., Kannourakis G., Zeidler C., Welte K., Benson K.F., Horwitz M., 2000. Mutations in the gene encoding neutrophil elastase in congenital and cyclic neutropenia. Blood, 96(7): 2317-2322.

Deordieva E., Shvets O., Voronin K., Maschan A., Welte K., Skokowa J., Novichkova G., Shcherbina A., 2021. Nicotinamide (vitamin B3) treatment improves response to G-CSF in severe congenital neutropenia patients. Br J Haematol, 192(4): 788-792.

Donadieu J., Beaupain B., Fenneteau O., Bellanne-Chantelot C., 2017. Congenital neutropenia in the era of genomics: classification, diagnosis, and natural history. Br J Haematol, 179(4): 557-574.

Furutani E., Newburger P.E., Shimamura A., 2019. Neutropenia in the age of genetic testing: Advances and challenges. Am J Hematol, 94(3): 384-393.

Gauthier-Vasserot A., Thauvin-Robinet C., Bruel A.L., Duffourd Y., St-Onge J., Jouan T., Riviere J.B., Heron D., Donadieu J., Bellanne-Chantelot C., Briandet C., Huet F., Kuentz P., Lehalle D., Duplomb-Jego L., Gautier E., Maystadt I., Pinson L., Amram D., El Chehadeh S., Melki J., Julia S., Faivre L., Thevenon J., 2017. Application of whole-exome sequencing to unravel the molecular basis of undiagnosed syndromic congenital neutropenia with intellectual disability. Am J Med Genet A, 173(1): 62-71.

Germeshausen M., Deerberg S., Peter Y., Reimer C., Kratz C.P., Ballmaier M., 2013. The spectrum of ELANE mutations and their implications in severe congenital and cyclic neutropenia. Hum Mutat, 34(6): 905-914.

Grenda D.S., Murakami M., Ghatak J., Xia J., Boxer L.A., Dale D., Dinauer M.C., Link D.C., 2007. Mutations of the ELA2 gene found in patients with severe congenital neutropenia induce the unfolded protein response and cellular apoptosis. Blood, 110(13): 4179-4187.

Ittiwut R., Sengpanich K., Lauhasurayotin S., Ittiwut C., Shotelersuk V., Sosothikul D., Suphapeetiporn K., 2020. Clinical and molecular characteristics of Thai patients with ELANE-related neutropaenia. J Clin Pathol, 75(2): 99-103.

Kostman R., 1975. Infantile genetic agranulocytosis. A review with presentation of ten new cases. Acta Paediatr Scand, 362-368.

Li H., Durbin R., 2010. Fast and accurate long-read alignment with Burrows-Wheeler transform. Bioinformatics, 26(5): 589-595.

Makaryan V., Zeidler C., Bolyard A.A., Skokowa J., Rodger E., Kelley M.L., Boxer L.A., Bonilla M.A., Newburger P.E., Shimamura A., Zhu B., Rosenberg P.S., Link D.C., Welte K., Dale D.C., 2015. The diversity of mutations and clinical outcomes for ELANE-associated neutropenia. Curr Opin Hematol, 22(1): 3-11.

McKenna A., Hanna M., Banks E., Sivachenko A., Cibulskis K., Kernytsky A., Garimella K., Altshuler D., Gabriel S., Daly M., DePristo M.A., 2010. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res, 20(9): 1297-1303.

McNulty S.N., Evenson M.J., Riley M., Yoest J.M., Corliss M.M., Heusel J.W., Duncavage E.J., Pfeifer J.D., 2021. A Next-Generation Sequencing Test for Severe Congenital Neutropenia: Utility in a Broader Clinicopathologic Spectrum of Disease. J Mol Diagn, 23(2): 200-211.

Nayak R.C., Trump L.R., Aronow B.J., Myers K., Mehta P., Kalfa T., Wellendorf A.M., Valencia C.A., Paddison P.J., Horwitz M.S., Grimes H.L., Lutzko C., Cancelas J.A., 2015. Pathogenesis of ELANE-mutant severe neutropenia revealed by induced pluripotent stem cells. J Clin Invest, 125(8): 3103-3116.

Nustede R., Klimiankou M., Klimenkova O., Kuznetsova I., Zeidler C., Welte K., Skokowa J., 2016. ELANE mutant-specific activation of different UPR pathways in congenital neutropenia. Br J Haematol, 172(2): 219-227.

Rydzynska Z., Pawlik B., Krzyzanowski D., Mlynarski W., Madzio J., 2021. Neutrophil Elastase Defects in Congenital Neutropenia. Front Immunol, 12(653932.

Scheike J.A., Baldauf C., Spengler J., Albericio F., Pisabarro M.T., Koksch B., 2007. Amide-to-ester substitution in coiled coils: the effect of removing hydrogen bonds on protein structure. Angew Chem Int Ed Engl, 46(41): 7766-7769.

Zhang J., Barbaro P., Guo Y., Alodaib A., Li J., Gold W., Ades L., Keating B.J., Xu X., Teo J., Hakonarson H., Christodoulou J., 2016. Utility of next-generation sequencing technologies for the efficient genetic resolution of haematological disorders. Clin Genet, 89(2): 163-172.




How to Cite

Anh Linh, D., Van Anh, N. T., Van Tung, N., Huy Hoang, N., Diem Ngoc, N., Phuong Mai, N. T., Manh Tien, N., & Thi Kim Lien, N. (2022). De novo mutations of \(\textit{ ELANE}\) gene in three Vietnamese patients with severe congenital neutropenia. Academia Journal of Biology, 44(3), 77–85.




Most read articles by the same author(s)