Korean J Lab Med.  2010 Apr;30(2):111-116. 10.3343/kjlm.2010.30.2.111.

Molecular Analysis of Two Cases of Severe Congenital Neutropenia

• Park J
• Kim M
• Lim J
• Kim Y
• Cho B
• Park YJ
• Han K

• KMID: 1096794
• DOI: http://doi.org/10.3343/kjlm.2010.30.2.111

Abstract

Severe congenital neutropenia is a rare hematological disease characterized by a selective decrease in circulating neutrophils, maturation arrest of granulocytic precursors at the promyelocyte stage, and recurrence of infections. A 2-month-old male infant (patient A) and a 14-month-old female child (patient B) were referred to our hospital due to severe neutropenia. Sequencing analysis of ELA2 and HAX1 genes was performed. Two single nucleotide polymorphisms of HAX1 gene were found. They were 5,104T-->G point mutation of exon 1 and 5,474A-->G point mutation of intron 1 in HAX1 gene. The mutation of ELA2 gene was not found. The patient A showed a good response to granulocyte colony-stimulating factor (G-CSF) treatment and the absolute neutrophil count recovered to 1,195/microliter. But the patient B showed a partial response to G-CSF treatment and experienced several episodes of herpetic gingivostomatitis, oral ulcer, acute pharyngotonsillitis and otitis media during follow-up.

Keyword

Severe congenital neutropenia; ELA2; HAX1

MeSH Terms

Adaptor Proteins, Signal Transducing/genetics
Bone Marrow/pathology
Female
Granulocyte Colony Stimulating Factor, Recombinant/adverse effects/therapeutic use
Humans
Infant
Male
Neutropenia/congenital/drug therapy/*genetics
Neutrophils/cytology/pathology
Oral Ulcer/etiology
Otitis Media/etiology
Polymorphism, Single Nucleotide
Serine Endopeptidases/genetics
Stomatitis, Herpetic/etiology

Figure

• 

  Fig. 1. Bone marrow smears show markedly decreased granulocytic precursors (A and C, Wright stain, ×400) and a few promyelocytes (B and D, Wright stain, ×1,000) in patient A and B, respectively.

• 

  Fig. 2. Sequencing analysis of HAX1. 5,104T→G point mutation of exon 1 (A, C) and 5,474A→G point mutation of intron 1 (B, D) in patient A and B, respectively. The point mutations of patient A are heterozygous and those of patient B are homozygous mutations.

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