조혈모세포이식 이후 발생한 UL97 유전자 597-600 해독틀내 결실이 있는 Ganciclovir 내성 거대세포바이러스 대장염 1예
The First Case of Ganciclovir-Resistant Cytomegalovirus Colitis with a 597-600 Deletion in UL97 Gene after Stem Cell Transplantation in Korea
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인간 거대세포바이러스(cytomegalovirus, CMV) 감염은 조혈모세포이식 환자에서 심각한 합병증을 일으킬 수 있다. 약제 내성 발생이 문제가 되는데 ganciclovir (GCV) 내성은 대부분 UL97 유전자의 돌연변이에 의해 발생하며 그 위치는 주로 코돈 460, 520, 590-607 등 세 가지로 알려져 있다. 저자들은 UL97의 코돈 597-600 결실에 의한 GCV 내성 CMV 대장염 환자를 보고하고자 한다. 46세 남자 환자가 골수이형성증후군으로 반일치 말초혈조혈모세포이식을 받았다. 이식 28일 째, CMV 항원 검사 결과 양성이 나와 GCV 치료를 시작하였고 12주간 지속하였으나 CMV 항원 검사 결과의 반응이 없고 CMV 대장염이 악화되었다. 직접염기서열분석법에 의해 UL97에서 코돈 597-600에 해독틀내 결실이 관찰되어 GCV 내성 CMV가 확인되었다. 치료약제는 foscarnet (FOS)로 변경하였고 CMV 항원검사는 두 번 연속적으로 음성 결과가 나왔으며 임상 증상도 호전되었다. 비록 CMV 대장염으로부터 환자는 회복되었지만, 이식 146일 째, 급성 간부전, 간신증후군, 패혈증 등으로 사망하였다. 본 증례는 국내 처음으로 CMV UL97의 코돈 597-600 결실을 보고하는 것이며 이 돌연변이로 인해 GCV 내성이 발생하였지만 FOS 감수성은 유지되는 것을 확인할 수 있었다. [Ann Clin Microbiol 2015;18:64-67]
Abstract
Human cytomegalovirus (CMV) infection has been a major concern in hematopoietic stem cell transplant recipients. Ganciclovir (GCV) resistance results mostly from mutations within the protein kinase UL97 gene. The three hot spots for GCV resistance (codons 460, 520, and 590-607) were well known. We describe a case of GCV-resistant CMV colitis caused by a 597-600 deletion in UL97 after haplo-identical peripheral blood stem cell transplantation (h-PBSCT) in a 46 year-old man with myelodysplastic syndrome. On post-PBSCT day 28, CMV antigenemia turned positive. Treatment of GCV was started and continued for 12 weeks but CMV antigenemia did not respond to the treatment and CMV colitis was worsened. The UL97 showed the in-frame deletion between codons 597 and 600 by direct sequencing. The treatment was switched to foscarnet and the antigenemia test was consecutively negative twice, and clinical symptoms improved. Despite the recovery of the patient from CMV colitis, the patient expired post-PBSCT day 146 from acute liver failure, hepatorenal syndrome and septic shock. This case is a first report of a deletion 597-600 in CMV UL97 in Korea. A 597-600 deletion in UL97 was responsible for the GCV resistance while preserving susceptibility to foscarnet. (Ann Clin Microbiol 2015;18:-67)
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