Novel mutations in unrelated Vietnamese patients with chronic granulomatous disease.

Autor: Binh NT; Pathophysiology and Immunology Department, Hanoi Medical University, 1 - Ton That Tung str., Dongda, Hanoi, Viet Nam; Hematology Department, Vietnam National Hospital of Pediatrics, 18/879 La Thanh str., Dongda, Hanoi, Viet Nam., Lien NTK; Institute of Genome Research, Vietnam Academy of Science and Technology, 18 - Hoang Quoc Viet str., Caugiay, Hanoi, Viet Nam., Anh NTV; Allergy, Immunology and Rheumatology Department, Vietnam National Hospital of Pediatrics, 18/879 La Thanh str., Dongda, Hanoi, Viet Nam., Mai NTP; Human Genetics Department, Vietnam National Hospital of Pediatrics, 879 La Thanh str., Dongda, Hanoi, Viet Nam., Ha NTV; Gastroenterology Department, Vietnam National Hospital of Pediatrics, 18/879 La Thanh str., Dongda, Hanoi, Viet Nam., Ha DT; Gastroenterology Department, Vietnam National Hospital of Pediatrics, 18/879 La Thanh str., Dongda, Hanoi, Viet Nam., Tung NV; Institute of Genome Research, Vietnam Academy of Science and Technology, 18 - Hoang Quoc Viet str., Caugiay, Hanoi, Viet Nam; Graduate University of Science and Technology, Vietnam Academy of Science and Technology, 18 - Hoang Quoc Viet str., Caugiay, Hanoi, Viet Nam., Hoang NH; Institute of Genome Research, Vietnam Academy of Science and Technology, 18 - Hoang Quoc Viet str., Caugiay, Hanoi, Viet Nam; Graduate University of Science and Technology, Vietnam Academy of Science and Technology, 18 - Hoang Quoc Viet str., Caugiay, Hanoi, Viet Nam. Electronic address: nhhoang@igr.ac.vn.
Jazyk: angličtina
Zdroj: Clinica chimica acta; international journal of clinical chemistry [Clin Chim Acta] 2022 Aug 01; Vol. 533, pp. 114-121. Date of Electronic Publication: 2022 Jun 18.
DOI: 10.1016/j.cca.2022.06.003
Abstrakt: Background: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder (PID) due to genetic defects in the NADPH oxidase of phagocytes. Affected patients become susceptible to infections such as pneumonia, diarrhea, and skin ulcer types. The patients require life-long treatment with prophylactic antibiotics, antifungals, or hematopoietic stem cell transplantation (HSCT) therapy. Early, accurate diagnosis will contribute to the life-prolonging of patients with CGD. This study's aim is to identify the mutation related to the disease.
Case Presentation: Six patients from different Vietnamese families were collected for genetic analysis at Allergy, Immunology, and Rheumatology Department, Vietnam National Hospital Pediatrics. They were diagnosed with CGD by flow cytometry test with the conversion of dihydrorhodamine (DHR) 123 to rhodamine 123.
Methods: We performed whole exome sequencing (WES) as a tool for detecting novel mutations. The mutations were confirmed by the Sanger sequencing method in patients and their families. The influence of the mutations was predicted with the in silico analysis tools: PROVEAN, SIFT, PolyPhen 2, Mutation Taster, and MaxEntScan.
Results: In this study, five mutations were found in six unrelated patients with CGD from different Vietnamese families. Three novel pathogenic mutations were detected including one mutation (c.45+2 T>G) in the CYBB gene and two mutations (c.187_188insA and c.289G>C) in the NCF2 gene.
Conclusions: Our results of CGD-related mutations contribute to the general understanding of the etiology of the disease and emphasize that WES sequencing can be used as a tool to help to diagnose carriers as well as assist in genetic counseling and prenatal screening.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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