Neutrophil function and molecular analysis in severe leukocyte adhesion deficiency type I without separation delay of...

Leukocyte adhesion deficiency type I (LAD I) is characterized by recurrent and fatal bacterial infections, and caused by the mutation of the CD18 gene. A 9-month-old infant whose umbilical cord separated at day 10 of life had sepsis, complicated otitis media and neutrophilia. Molecular analysis showed homozygous intron 7 (+1) g > a in the CD18 gene, resulting in three splicing transcriptions that inserted 64, 298 (5' end of intron 7), and 1157 (whole intron 7) nucleotides into the 300th amino acid of Ile and stopped at the 326th (inserted 64 and 1157 nucleotides) and the 344th (inserted 64 nucleotides), respectively. The two truncated mutations lost cysteine-rich, transmembrane, and cytoplasma domains. Increased susceptibility to infections correlated to polymorphonuclear cell dysfunction, including absent expression of adhesion molecule (CD11b/CD18), impaired chemotaxis, and decreased phagocytosis. Both his heterozygous parents revealed non-random skewing only to the wild type. The skewing pattern and severe phenotype make stem cell transplantation an optimal option.