Suksawat Y, Pacharn P, Siripipattanamongkol N, Boonyawat B. Three novel homozygous ITGB2 mutations among two patients with leukocyte adhesion defect type-1: Two case reports. World J Clin Pediatr 2022; 11(5): 429-436 [PMID: 36185095 DOI: 10.5409/wjcp.v11.i5.429]
Corresponding Author of This Article
Yiwa Suksawat, MD, Doctor, Division of Allergy and Immunology, Department of Pediatrics, Phramongkutklao Hospital and Phramongkutklao College of Medicine, 315 Rajavithi Road, Ratchathewi, Bangkok 10400, Thailand. yiwasuksawat@pcm.ac.th
Research Domain of This Article
Genetics & Heredity
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/
Yiwa Suksawat, Division of Allergy and Immunology, Department of Pediatrics, Phramongkutklao Hospital and Phramongkutklao College of Medicine, Bangkok 10400, Thailand
Punchama Pacharn, Division of Allergy and Immunology, Department of Pediatrics, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
Nunthana Siripipattanamongkol, Division of Allergy and Immunology, Department of Pediatrics, Chiangrai Prachanukroh Regional Hospital, Chiangrai 57000, Thailand
Boonchai Boonyawat, Division of Medical Genetics, Department of Pediatrics, Phramongkutklao Hospital and Phramongkutklao College of Medicine, Bangkok 10400, Thailand
Author contributions: Suksawat Y, Siripipattanamongkol N and Boonyawat B contributed to the drafting and writing of the case report manuscript and were involved in the clinical care of the patients; Boonyawat B extracted genomic DNA and performed genetic studies; Pacharn P supervised and edited the manuscript; all authors approved the final draft of the manuscript.
Informed consent statement: Informed written consent was obtained from the patient for publication of this report and any accompanying images.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yiwa Suksawat, MD, Doctor, Division of Allergy and Immunology, Department of Pediatrics, Phramongkutklao Hospital and Phramongkutklao College of Medicine, 315 Rajavithi Road, Ratchathewi, Bangkok 10400, Thailand. yiwasuksawat@pcm.ac.th
Received: April 22, 2022 Peer-review started: April 22, 2022 First decision: May 31, 2022 Revised: June 10, 2022 Accepted: August 22, 2022 Article in press: August 22, 2022 Published online: September 9, 2022 Processing time: 138 Days and 6.6 Hours
Abstract
BACKGROUND
A leukocyte adhesion defect (LAD) is a rare primary immunodeficiency disorder. LAD type 1 (LAD-1) is the most common, which is caused by ITGB2 mutation resulting in dysfunction of β2 integrin, which impairs leukocyte adherence to the endothelium.
CASE SUMMARY
The first two cases of LAD-1 in Thailand presented with recurrent omphalitis, soft tissue infection, marked leukocytosis, and neutrophilia. One patient experienced delayed umbilical cord separation. Mutation analysis was performed by direct DNA sequencing of the ITGB2 gene. The results revealed two novel homozygous missense mutations, c.920C>T (p.Leu307Pro) in exon 8 and c.758G>A (p.Arg253His) in exon 7, and one novel homozygous nonsense mutation, c.262C>T (p.Gln88Ter) in exon 4, in the genomic DNA of the first and second patients, respectively. Heterozygous mutations were identified in the parents of both patients, suggesting a carrier status. The patients were administered intravenous antibiotics for infections with good clinical responses. Hematopoietic stem cell transplantation could not be performed due to the unavailability of matched donors. However, a significant decline in infections was observed after antibiotic prophylaxis. Several follow-up visits were conducted for both patients. They are currently 6 years old.
CONCLUSION
Molecular analysis is essential for definitive diagnosis, early treatment implementation, and prevention of LAD-1 in future pregnancy.
Core Tip: Leukocyte adhesion defect (LAD) is a rare autosomal recessive primary immunodeficiency disorder characterized by defects in the leukocyte recruitment cascade. LAD type 1, caused by a mutation in ITGB2, is the most common form. Here, we report the first two cases of LAD type 1 with a molecularly confirmed ITGB2 mutation in Thailand. At the time of initial presentation, both patients had recurrent omphalitis, bacterial soft tissue infection, and marked leukocytosis. Molecular analysis revealed two missense variants and one nonsense mutation. Early identification of these patients by molecular analysis was proven essential for definitive diagnosis, proper antibiotic prophylaxis, and initiation of matched donor hematopoietic stem cell transplantation.
