The family pedigree and the IL-7Rα sequences.

(A) The family pedigree showing an inbred family with consanguinity across 5 generations. Information concerning early infant deaths or severe combined immunodeficiency could only be obtained for the 2 most recent generations. Patients 1(I-2) and 2 (I-3) and one of their cousins (II-5) (solid black symbols) were diagnosed with SCID. Three other male cousins (II-1-3) (gray symbols) died in infancy from severe infections consistent with SCID. (B) IL-7Rα sequences from the affected family. IL-7Rα exons were isolated from genomic DNA by PCR and directly sequenced. Patients 1, 2, and 3 were homozygous for a C to T transition at nucleotide 394 in exon 4, leading to a proline to serine substitution (P132S) in the extracellular domain of IL-7R. The sibling of patient 1 and 2 and their parents harbored both wild and mutant alleles. In contrast to this family, IL-7R sequences from 60 unrelated control individuals failed to show any alteration to the normal sequence in exon 4.