학술논문
Investigation of ITGB2 Gene in 12 New Cases of Leukocyte Adhesion Deficiency-Type I Revealed Four Novel Mutations from Iran.
Document Type
Article
Author
Mortezaee, Fatemeh Taghizade; Esmaeli, Behnaz; Badalzadeh, Mohsen; Ghadami, Mohsen; Fazlollahi, Mohammad Reza; Alizade, Zahra; Hamidieh, Amir Ali; Chavoshzadeh, Zahra; Movahedi, Masoud; Heydarzadeh, Marzieh; Shabestari, Mahnaz Sadeghi; Tavassoli, Mahmoud; Nabavi, Mohammad; Kalmarzi, Rasoul Nasiri; Pourpak, Zahra
Source
Subject
*DNA analysis
*AGE factors in disease
*CELL adhesion molecules
*FLOW cytometry
*GENETICS
*IMMUNOLOGICAL deficiency syndromes
*GENETIC mutation
*POLYMERASE chain reaction
*RESEARCH funding
*PHENOTYPES
*SEQUENCE analysis
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Language
ISSN
1029-2977
Abstract
Background: Leukocyte adhesion deficiency type I (LAD-I) is a rare, autosomal recessive inherited immunodeficiency disease. LAD-I is caused by mutations in the ITGB2 gene and characterized by recurrent severe bacterial infections, as well as impaired wound healing with lack of pus formation. Methods: In this study, we investigated /TG62 gene mutations in 12 patients and their parents. Genomic DNA was extracted from whole blood samples. All coding regions of the ITGB2 gene were amplified using PCR and followed by direct sequencing. Results: Genetic analysis revealed 12 different homozygous mutations, including six missense (c.382G>A, c.2146G>C, c.715G>A, C.691OC, C.1777C and new C.1686OA), two new nonsense (c.1336G>T and C.1821OA), three-frame shift (c.1143delc, c.1907delA and new c.474dupC) and a splice site (c.1877+2T>C). Flow cytometry analysis of CD11/CD18 expression on neutrophils revealed defect in CD18 in all twelve cases (1.4% to 42%), CD11a in ten cases (0.1% to 26.7%), CD11b in nine cases (1.2% to 58.8%), and CD11c in all cases (0% to 18.1 %). The patients' parents were both heterozygous carriers. Conclusion: Our findings showed four new mutations in the ITGB2 gene. These results can be used for decisive genetic diagnosis, genetic counseling, as well as prenatal diagnosis for all patients who are suspended to LADI. [ABSTRACT FROM AUTHOR]