Novel ITGB2 Mutation Is Responsible for a Severe Form of Leucocyte Adhesion Deficiency Type 1.

Leukocyte adhesion deficiency type 1 (LAD1) is a rare autosomal recessive hereditary disorder characterized by recurrent infections, impaired pus formation, delayed wound healing, omphalitis, and delayed separation of the umbilical cord as hallmark features of the disease. It results from mutations...

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Published in:BioMed Research International pp. 1 - 9
Main Authors: Bouhouche, Ahmed, Tabache, Yasmin, Askander, Omar, Charoute, Hicham, Mesnaoui, Nada, Belayachi, Lamiae, El Hafidi, Naima, Hardizi, Houyam, El Fahime, Elmostafa, Erreimi, Naima, Barakat, Abdelhamid, Khattab, Mohammed, Seghrouchni, Fouad, El Hassani, Amine
Format: pictorial research tables/charts Journal Article
Published: Wiley-Blackwell 3/3/2022
Online Access:View this record in EBSCOhost
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      dt: 3/3/2022
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      pub: Wiley-Blackwell
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        10.1155/2022/1141280
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        atl: Novel ITGB2 Mutation Is Responsible for a Severe Form of Leucocyte Adhesion Deficiency Type 1.
      aug:
        au:
          Bouhouche, Ahmed
          Tabache, Yasmin
          Askander, Omar
          Charoute, Hicham
          Mesnaoui, Nada
          Belayachi, Lamiae
          El Hafidi, Naima
          Hardizi, Houyam
          El Fahime, Elmostafa
          Erreimi, Naima
          Barakat, Abdelhamid
          Khattab, Mohammed
          Seghrouchni, Fouad
          El Hassani, Amine
        affil: Research Team in Neurology and Neurogenetics, Genomics Center of Human Pathologies, Medical School and Pharmacy, Mohammed V University in Rabat, Morocco
      sug:
        subj:
          Leukocytes Physiopathology
          Immunologic Deficiency Syndromes Risk Factors
          Genes
          Mutation
          Human
          Male
          Infant
          Mauritania
          Phenotype
          Flow Cytometry
          Sequence Analysis
          Molecular Diagnostic Techniques
          Receptors, Cell Surface
          Infant: 1-23 months
          Male
      ab: Leukocyte adhesion deficiency type 1 (LAD1) is a rare autosomal recessive hereditary disorder characterized by recurrent infections, impaired pus formation, delayed wound healing, omphalitis, and delayed separation of the umbilical cord as hallmark features of the disease. It results from mutations in the integrin β2 subunit gene ITGB2, which encodes the integrin beta chain-2 protein CD18. In this study, we aimed to investigate the case of a five-month-old boy who presented with a clinical phenotype and flow cytometry results suggesting LAD1 disease. Sanger sequencing of all exons and intron boundaries of ITGB2 identified a novel in-frame deletion in exon 7 (ITGB2 c.844_846delAAC, p.Asn282del) in the patient. The p.Asn282del mutation was heterozygous in the child's parents, whereas it was absent in the 96 control individuals from North Africa. This variant was evaluated by two in silico mutation analysis tools, PROVEAN and MutationTaster, which predicted that the mutation was likely to be pathogenic. In addition, molecular modeling with the YASARA View software suggested that this novel mutation may affect the structure of integrin beta-2 and, subsequently, its interaction with integrin alpha-X. In summary, we report a novel pathogenic mutation p.Asn282del associated with LAD1 that expands the mutation diversity of ITGB2 and suggest the combination of flow cytometry and ITGB2 sequencing as a first-line diagnostic approach for LAD disease.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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