Characterization of 11 New Cases of Leukocyte Adhesion Deficiency Type 1 with Seven Novel Mutations in the ITGB2 Gene

Infectious Disease Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Journal of Clinical Immunology (Impact Factor: 3.18). 09/2010; 30(5):756-60. DOI: 10.1007/s10875-010-9433-2
Source: PubMed


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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    • "ITGB2 gene mutations are heterogeneous and majority of them are located in highly conserved domain, Von Willebrand Factor type A (VWFA), of β2 integrin subunit [4, 5, 24]. This highly conserved domain is coded by exons 5–9 of the gene [17] and required for the common enzyme activity. According to the Human Gene Mutation Database (HGMD®,, more than 100 mutations have been identified in "
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    ABSTRACT: Leukocyte adhesion deficiency type 1 (LAD1) is an autosomal recessive disorder clinically characterized by severe, recurrent bacterial infections, impaired pus formation and wound healing. It is caused by mutation in the ITGB2 gene, encoding the β2 integrin subunit of the leukocyte adhesion cell molecule. This study aimed to identify disease causing mutations in 19 consanguineous families diagnosed with LAD1. Blood samples were collected after informed and written consent was obtained. Genomic DNA was extracted from peripheral blood of patients and their parents. PCR amplification of the ITGB2 gene was done using specific primers followed by sequencing for mutation detection. A total number of 14 alterations scattered throughout the ITGB2 gene were ascertained in which 10 mutations were previously reported, including c.329-6C>A, c.382G>T, c.715G>A, c.843delC, c.897+1G>A, c.1062A>T, c.1143delC, c.1877+2T>C, c.1907delA and c.2147G>C. Four novel likely pathogenic mutations consisting of c.576dupC (Asn193GlnfsX72), c.706G>A (Gly236Arg), c.897+1G>T and c.1030G>T (Glu344∗), were identified. The majority of these mutations were located in exon six, suggesting this exon as a hotspot region probably. This study emphasis on allelic heterogeneity of the ITGB2 gene in Iranian patients diagnosed with LAD1. Our results suggest that every population should develop a mutation database for rare genetic disorders to take advantage in genetic counseling clinic as well as genetic testing for rapid diagnostic purposes.
    No preview · Article · Nov 2015 · Human Immunology
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    • "c.742-13G/A NA [3] [22] c.810G/A p.Ala270Ala (silent) [Ensembl] c.819A/G p.Gly273Gly (silent) [3,5,22,25,31,38,45] [Ensembl] c.849C/T p.Asp283Asp (silent) [Ensembl] c.892G/A p.Glu298Lys [58] c.906A/G p.Pro302Pro (silent) [Ensembl] c.993 + 41T/C NA Unpubl. c.994-47G/A a NA [3] [22] [24] c.1002C/T p.Thr334Thr (silent) [Ensembl] c.1062T/A p.His354Gln [30] [48] c.1101C/A p.Val367Val (silent) [3] [22] [24] [25] [30] [37] [58] c.1146C/T p.Tyr382Tyr (silent) [Ensembl] c.1186C/T p.Pro396Ser [Ensembl] c.1224 + 48G/T NA [3] [22] c.1247C/T p.Thr416Met [Ensembl] c.1323C/T p.Val441Val (silent) [3] [5] [22] [24] [25] [30] [37] [58] c.1497G ? A p.Lys499Lys (silent) [Ensembl] c.1542C/T p.Cys514Cys (silent) [Ensembl] c.1635C/T p.Asn545Asn (silent) [Ensembl] c.1700G/C p.Gly567Ala [58] c.1714G/T p.Ala572Ser [58] c.1724G/C p.Cys575Ser [58] c.1756C/T p.Arg586Trp [3–5,58,59] c.1793G/T p.Cys598Phe [Ensembl] c.1888G/A p.Glu630Lys [Ensembl] c.1893C/T p.Cys631Cys (silent) [Ensembl] c.2058C/G p.Leu686Leu (silent) [Ensembl] "
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