Clinical and molecular characteristics of Thai patients with related neutropaenia.

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 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 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 gene, suggesting it the most common associated with the disease. Two novel mutations were also identified, expanding the genotypic spectrum of .