Characterization of 11 new cases of leukocyte adhesion deficiency type 1 with seven novel mutations in the ITGB2 gene

J Clin Immunol. 2010 Sep;30(5):756-60. doi: 10.1007/s10875-010-9433-2. Epub 2010 Jun 12.

Abstract

Background: 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.

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • DNA Mutational Analysis
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Gram-Negative Bacterial Infections / etiology
  • Gram-Negative Bacterial Infections / genetics*
  • Gram-Negative Bacterial Infections / physiopathology
  • Humans
  • Infant
  • Iran
  • Leukocyte-Adhesion Deficiency Syndrome / complications
  • Leukocyte-Adhesion Deficiency Syndrome / genetics
  • Leukocyte-Adhesion Deficiency Syndrome / physiopathology
  • Male
  • Molecular Sequence Data
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • Mutation / genetics
  • Recurrence
  • Skin Ulcer / etiology
  • Skin Ulcer / genetics*
  • Skin Ulcer / physiopathology
  • Umbilical Cord / immunology*
  • Umbilical Cord / microbiology
  • Umbilical Cord / pathology

Substances

  • Cytoskeletal Proteins
  • ITGB1BP2 protein, human
  • Muscle Proteins

Supplementary concepts

  • Leukocyte adhesion deficiency type 1