A novel 3′ splice-site mutation and a novel gross deletion in leukocyte adhesion deficiency (LAD)-1

► We performed molecular analysis on an LAD-I patient. ► We found and characterized two novel ITGB2 mutations; paternal: g.43201_PTTG1IP:10890del27703; maternal: g.23457C>A. ► g.43201_PTTG1IP:10890del27703 spanned from intron 11 of ITGB2 to intron 2 of PTTG1IP, resulting in a detectable hybrid mRNA product. ► g.23457C>A caused a novel splice mutation through activation of a cryptic 3′ splice site at intron 2 to include 43 intronic nucleotides (r.[59-43_59-1ins;59-10C>A]). ► Further analysis suggests that the cryptic 3′ splice site at −43 was selected over a putative cryptic at +11 due to the lack of an upstream AG dinucleotide. A patient was diagnosed with leukocyte adhesion deficiency-1. She was born in 1996 and her parents are not known to be related. Her leukocytes expressed less than 2% of the CD18 antigens relative to normal individuals. Molecular analysis revealed that she is a compound heterozygote. She inherited a 27,703 bp deletion from her father (g.43201_PTTG1IP:10890del27703), spanning from intron 11 of the gene for the β2 integrin (ITGB2, CD18, NG_007270.2) to intron 2 of the gene for the Pituitary Tumor-Transforming Gene 1 Interacting Protein (PTTG1IP, NC_000021.8). The maternal allele has a g.23457C>A mutation at position −10 in intron 2 of the ITGB2 gene, resulting in the activation of a cryptic 3′ splice site in intron 2 to include 43 intronic nucleotides (r.[59-43_59-1ins;59-10C>A]).