Characterization of 11 New Cases of Leukocyte Adhesion Deficiency Type 1 With Seven Novel Mutations in the Itgb2 Gene Publisher Pubmed



Parvaneh N^{1, 2, 3} ; Mamishi S^{1, 2} ; Rezaei A² ; Rezaei N^{2, 3} ; Tamizifar B⁴ ; Parvaneh L⁵ ; Sherkat R⁶ ; Ghalehbaghi B⁷ ; Kashef S⁸ ; Chavoshzadeh Z⁹ ; Isaeian A² ; Ashrafi F¹⁰ ; Aghamohammadi A^{2, 3} Show Affiliations
Source: Journal of Clinical Immunology Published:2010

Abstract

Background: Leukocyte adhesion deficiency type 1 (LAD I) is an autosomal recessive disorder caused by mutations in the ITGB2 gene, encoding the β2 integrin family. Severe recurrent infections, impaired wound healing, and periodontal diseases are the main features of disease. Methods: In order to investigate clinical and molecular manifestations of new LAD I cases, 11 patients diagnosed in one center during 7 years were studied. Patients were screened for the ITGB2 gene mutations, using polymerase chain reaction, followed by single-strand conformation polymorphism and sequencing. Results: The most common first presenting feature of the patients was omphalitis. The mean age of cord separation was 19.9 ± 1 days. The most common clinical manifestations of the patients during the follow-up period included omphalitis, skin ulcers with poor healing, sepsis, and otitis media. During the follow-up, eight patients died. Eight homozygous changes, including seven novel mutations, were detected: two splicing (IVS4-6C>A, IVS7+1G>A), three missense (Asp128Tyr, Ala239Thr, and Gly716Ala), and three frameshift deletions (Asn282fsX41, Tyr382fsX9, and Lys636fsX22). Conclusion: Our results indicate that different mutations underlie the development of LAD I. Definitive molecular diagnosis is valuable for genetic counseling and prenatal diagnosis. Regarding clinical presentations, it seems that omphalitis is the most consistent finding seen in LAD I infants. © 2010 Springer Science+Business Media, LLC.