Characterization of 11 new cases of leukocyte adhesion deficiency type 1 with seven novel mutations in the ITGB2 gene.
ABSTRACT Leukocyte adhesion deficiency type 1 (LAD I) is an autosomal recessive disorder caused by mutations in the ITGB2 gene, encoding the beta2 integrin family. Severe recurrent infections, impaired wound healing, and periodontal diseases are the main features of disease.
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.
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).
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.
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ABSTRACT: Leucocyte adhesion deficiency type 1 (LAD-1) is a rare autosomal recessive primary immunodeficiency disorder, characterised by the absence or deficient expression of the adhesion molecules on leucocytes. The disease is usually associated with leucocytosis, recurrent severe bacterial and fungal infections without pus formation and impaired wound healing. Omphalitis, delayed umbilical cord separation, perirectal abscess, sepsis, necrotising enterocolitis, pneumonia, gingivitis and periodontitis are common features of disease.1---3 Although some forms of primary immunodeficiency diseases could develop malignancies, there is no report of non-Hodgkin’s lymphoma in patients with LAD.Allergologia et Immunopathologia 05/2013; · 1.23 Impact Factor
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ABSTRACT: Primary immunodeficiency diseases (PID) comprise a heterogeneous group of inherited diseases with a wide spectrum of clinical manifestations and laboratory abnormalities. Definite diagnosis of a PID is performed most reliably by detection of a gene mutation which will allow genetic counseling. In addition, detection and confirmation of PIDs that were not severe enough during childhood to lead to a specific diagnosis would be possible. As a definite diagnosis of PID is of importance for the management of these disorders, we present a review on studies that have investigated mutations among patients with different types of PID in Iran. Although the frequency of a definite molecular diagnosis of PID in Iran is acceptable in a developing country, we believe that providing additional laboratory resources and diagnostic methods, development of specialized centers for PID, in addition to improvement of physicians' awareness, may facilitate clinical and genetic diagnosis of patients with PID in Iran.Expert Review of Clinical Immunology 01/2014; · 3.34 Impact Factor
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ABSTRACT: Primary immunodeficiency diseases (PID) are a group of inherited disorders characterized by recurrent infections, and in many cases autoimmunity and malignancies. A number of PID patients suffer from a variety of ocular manifestations. Although these associated ocular features are not common, awareness combined with better understanding of the contributing mechanisms will allow prompt diagnosis and specific treatment, leading to reduction or prevention of serious visual morbidities.Journal of Clinical Immunology 11/2013; 34(1). · 2.65 Impact Factor