Aims Congenital neutropaenia is a rare inherited disorder that mainly affects neutrophils causing severe infection. Mutations in several genes have been implicated in the disease pathogenesis. The genetic defects may vary in different populations, influenced by ethnicity and geographical location. Here we describe the clinical and genotypic characteristics of seven unrelated Thai cases with congenital neutropaenia.
Methods Seven unrelated patients with congenital neutropaenia were enrolled (5 female and 2 male) at King Chulalongkorn Memorial Hospital, Bangkok, Thailand. Clinical and laboratory data were collected. Whole exome sequencing (WES) analysis was performed in all cases.
Results WES successfully identified disease-causing mutations in the ELANE gene in all cases, including two novel ones: a heterozygous 12 base pair (bp) inframe insertion (c.289_300dupCAGGTGTTCGCC; p.Q97_A100dup) and a heterozygous 18 bp inframe deletion (c.698_715delCCCCGGTGGCACAGTTTG; p.A233_F238delAPVAQF). Five other previously described ELANE mutations (p.Arg103Pro, p.Gly214Arg, p.Trp241X, p.Ser126Leu and p.Leu47Arg) were also detected.
Conclusions All Thai patients with congenital neutropaenia in this study harboured causative mutations in the ELANE gene, suggesting it the most common associated with the disease. Two novel mutations were also identified, expanding the genotypic spectrum of ELANE.
- haematological diseases
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Handling editor Mary Frances McMullin.
RI and KuS contributed equally.
Contributors RI performed the research and drafted the manuscript. KuS collected the clinical data and drafted the manuscript. SL, DS and KaS collected and analysed all the clinical and sequencing data. CI analysed the sequencing data. VS, DS and KaS designed the study and wrote the manuscript. All authors have read and approved the final manuscript.
Funding This work was supported by Rachadapiseksompotch Fund (RA59/010) and the Special Task Force for Activating Research (STF 6300430003-1), Center of Excellence for Medical Genomics, Medical Genomics Cluster, Faculty of Medicine, Chulalongkorn University, the Thai Society of Hematology, Thailand Research Fund (BRG5980001; DPG6180001) and Health Systems Research Institute.
Competing interests None declared.
Patient consent for publication Parental/guardian consent obtained.
Ethics approval The study was approved by the institutional review board (RA59/010) of the Faculty of Medicine, Chulalongkorn University, Thailand.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available upon reasonable request. All data relevant to the study are included in the article.
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