Liu XY, Nie YB, Chen XJ, Gao XH, Zhai LJ, Min FL. Adult onset type 2 familial hemophagocytic lymphohistiocytosis with PRF1 c.65delC/c.163C>T compound heterozygous mutations: A case report. World J Clin Cases 2021; 9(10): 2289-2295 [PMID: 33869605 DOI: 10.12998/wjcc.v9.i10.2289]
Corresponding Author of This Article
Feng-Ling Min, MD, Chief Doctor, Professor, Department of Hematology, The Affiliated Hospital of Yangzhou University, Yangzhou University, No. 368 Hanjiang Middle Road, Yangzhou 225000, Jiangsu Province, China. 1014121694@qq.com
Research Domain of This Article
Hematology
Article-Type of This Article
Case Report
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Clin Cases. Apr 6, 2021; 9(10): 2289-2295 Published online Apr 6, 2021. doi: 10.12998/wjcc.v9.i10.2289
Adult onset type 2 familial hemophagocytic lymphohistiocytosis with PRF1 c.65delC/c.163C>T compound heterozygous mutations: A case report
Xin-Yi Liu, Yan-Bo Nie, Xue-Jing Chen, Xiao-Hui Gao, Li-Jia Zhai, Feng-Ling Min
Xin-Yi Liu, Xiao-Hui Gao, Li-Jia Zhai, Feng-Ling Min, Department of Hematology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou 225000, Jiangsu Province, China
Yan-Bo Nie, Gene Sequencing Laboratory, Tianjin SINO-US-Diagnostics Co.Ltd, Tianjin 300000, China
Author contributions: Liu XY and Min FL conceived and designed the study; Gao XH and Zhai LJ provided the tissue samples and supplied the clinical and pathological information of the patient; Nie YB performed data analysis of Sanger sequences and next-generation sequencing; Chen XJ performed flow cytometry analysis; Liu XY, Min FL, and Nie YB drafted and revised the manuscript; All authors read and approved the final manuscript.
Supported bythe Project of Key Talents of Strengthening Health through Science and Education of Yangzhou City, China, No. ZDRC201813.
Informed consent statement: The patient and his parents provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All the authors declare that they have no conflicting interests (including but not limited to commercial, personal, political, intellectual or religious interests) that are related to the work submitted for consideration of publication.
CARE Checklist (2016) statement: The guidelines of the “CARE Checklist-2016: Information for writing a case report” have been adopted.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Feng-Ling Min, MD, Chief Doctor, Professor, Department of Hematology, The Affiliated Hospital of Yangzhou University, Yangzhou University, No. 368 Hanjiang Middle Road, Yangzhou 225000, Jiangsu Province, China. 1014121694@qq.com
Received: September 19, 2020 Peer-review started: September 19, 2020 First decision: January 7, 2021 Revised: January 19, 2021 Accepted: February 1, 2021 Article in press: February 1, 2021 Published online: April 6, 2021 Processing time: 192 Days and 2.6 Hours
Abstract
BACKGROUND
Familial hemophagocytic lymphohistiocytosis (FHL) is a primary immunodefici-ency disease caused by gene defects. The onset of FHL in adolescents and adults may lead clinicians to ignore or even misdiagnose the disease. To the best of our knowledge, this is the first report to detail the clinical features of type 2 FHL (FHL2) with compound heterozygous perforin (PRF1) defects involving the c.163C>T mutation, in addition to correlation analysis and a literature review.
CASE SUMMARY
We report a case of a 27-year-old male patient with FHL2, who was admitted with a persistent fever and pancytopenia. Through next-generation sequencing technology of hemophagocytic lymphohistiocytosis (HLH)-related genes, we found compound heterozygous mutations of PRF1: c.65delC (p.Pro22Argfs*29) (frameshift mutation, paternal) and c.163C>T (p.Arg55Cys) (missense mutation, maternal). Although he did not receive hematopoietic stem cell transplantation, the patient achieved complete remission after receiving HLH-2004 treatment protocol. To date, the patient has stopped taking drugs for 15 mo, is in a stable condition, and is under follow-up observation.
CONCLUSION
The delayed onset of FHL2 may be related to the PRF1 mutation type, pathogenic variation pattern, triggering factors, and the temperature sensitivity of some PRF1 mutations. For individual, the detailed reason for the delay in the onset of FHL warrants further investigation.
Core Tip: In familial hemophagocytic lymphohistiocytosis (FHL), the perforin (PRF1): c.163C>T mutation is rare and the clinical features have not been reported. We discuss a case of adult onset type 2 FHL with PRF1 c.65delC/c.163C>T compound heterozygous mutations, and conduct a predictive analysis of the effects of the two mutations on PRF1 function and disease onset.
