Investigation of ITGB2 gene in 12 new cases of leukocyte adhesion deficiency-type I revealed four novel mutations from Iran.
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 ITGB2 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.691G>C, c.1777C and new c.1686C>A), two new nonsense (c.1336G>T and c.1821C>A), 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.


CONCLUSIONS
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.
Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Fatemeh
F
Taghizade Mortezaee
Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Behnaz
B
Esmaeli
Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Mohsen
M
Badalzadeh
Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Mohsen
M
Ghadami
Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Mohammad Reza
MR
Fazlollahi
Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Zahra
Z
Alizade
Hematology Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Amir Ali
AA
Hamidieh
Department of Pediatrics, Mofid Children Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Zahra
Z
Chavoshzadeh
Department of Allergy and Clinical Immunology, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
Masoud
M
Movahedi
Department of Pediatrics, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran.
Marzieh
M
Heydarzadeh
Tuberculosis and Lung Research Center of Tabriz, Children Hospital ,Tabriz University of Medical Sciences, Tabriz, Iran.
Mahnaz
M
Sadeghi Shabestari
Isfahan University of Medical Sciences, Isfahan, Iran.
Mahmoud
M
Tavassoli
Department of Allergy and Clinical Immunology, Rasool-e-Akram Hospital, Iran University of Medical Sciences, Tehran, Iran.
Mohammad
M
Nabavi
Department of Pediatrics, Kurdistan University of Medical Sciences, Sanandaj, Iran.
Rasoul
R
Nasiri Kalmarzi
Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran. Pourpakz@tums.ac.ir.
Zahra
Z
Pourpak
D018821:CD18 Antigens / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005260:Female; D005820:Genetic Testing; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007223:Infant; D007492:Iran; D018370:Leukocyte-Adhesion Deficiency Syndrome / Q000235:genetics*; D008297:Male; D011247:Pregnancy
D018821:CD18 Antigens; D018389:Codon, Nonsense