J Korean Med Sci.  2014 Mar;29(3):452-455. 10.3346/jkms.2014.29.3.452.

Different Clinical Phenotypes in Familial Severe Congenital Neutropenia Cases with Same Mutation of the ELANE Gene

• Cho HK
• Jeon IS

• KMID: 1734937
• DOI: http://doi.org/10.3346/jkms.2014.29.3.452

Abstract

Severe congenital neutropenia (SCN) is a heterogeneous group of disorders with a defect in granulopoiesis causing marked neutropenia and severe bacterial infections. A 17-month-old girl (patient 1) was admitted due to cervical lymphadenitis caused by methicillin-resistant Staphylococcus aureus, with neutropenia. She had Pseudomonas aeruginosa sepsis and peritonitis with perforated appendicitis at 8-month of age. Her sister, a 37-month-old girl (patient 2), had recurrent stomatitis with profound neutropenia, and her mother, a 32-yr-old woman (patient 3), had had recurrent stomatitis until her early 20s with neutropenia. We found an ELANE gene mutation (c.597+1G > A) from them in direct DNA sequencing analysis. Patients 1 and 2 did not respond to granulocyte colony stimulating factor and patient 1 was treated with prolonged antibiotics and excision. We demonstrated inherited SCN cases showing different severity even with the same mutation of the ELANE gene in a family.

Keyword

Severe Congenital Neutropenia; Neutrophil Elastase; Infection

MeSH Terms

Adult
Child, Preschool
DNA Mutational Analysis
Female
Granulocyte Colony-Stimulating Factor/therapeutic use
Humans
Infant
Leukocyte Elastase/*genetics
Methicillin-Resistant Staphylococcus aureus/isolation & purification
Mutation/genetics
Neutropenia/*congenital/diagnosis/drug therapy/genetics
Pedigree
*Phenotype
Polymorphism, Single Nucleotide
Recurrence
Staphylococcal Infections/diagnosis/microbiology
Stomatitis/diagnosis
Tomography, X-Ray Computed
Granulocyte Colony-Stimulating Factor
Leukocyte Elastase

Figure

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  Fig. 1 The contrast enhanced computed tomography of her neck revealed multiple enlarging lymph nodes with some necrotic changes in her left neck lymph node level II and V involving overlying skin, subcutaneous tissues and paraspinal muscles on the left (arrow), instead of significant abscess formation.

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  Fig. 2 Pedigree of this family shows their neutropenia has autosomal-dominant inheritance. The filled circles (female) represent the patients with severe congenital neutropenia. Other family members are not affected.

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  Fig. 3 Light microscopic examination of the bone marrow aspirate smear. (A) Myeloid cells are markedly decreased in number with left-shifted maturation showing maturation arrest at the promyelocyte stage (Wright stain, ×400). (B) Myeloblasts and promyelocytes showed prominent vacuolations and aberrations of azurophilic granules, while mature neutrophils are absent (Wright stain, ×1,000).

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  Fig. 4 Direct DNA sequencing analysis demonstrated an ELANE gene mutation, a substitution of the 597th base (G to A) in intron 4 (c.597+1G>A), in patients 1, 2 (her second elder sister), and 3 (her mother), but not in her father and her eldest sister.

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