Family pedigrees, haplotype analysis of polymorphic markers spanning the perforin locus on chromosome 10q21, and mutation detection in the perforin gene. (A) Affected patients are homozygous at the perforin locus for all the markers tested. The same alleles of the markers spanning the perforin locus were inherited by patients 1 and 2, who belong to 2 different families. The same mutation was identified as homozygous (**) in the patients and heterozygous (*) in their parents and some of their siblings. (B) Schematic representation of the perforin protein. The open box represents the calcium-binding domain (C2) and the dashed box represents the C-terminal part of the protein that is cleaved during protein maturation. The missense mutation identified in the patients' perforin C2 domain is shown.