Abstract We report here that a defect of the interleukin common gamma subunit (c) in X-linked severe combined immunodeficiency (XSCID) previously known as a missense mutation resulted instead in exon skipping in a Japanese XSCID patient. The phenotype of the patient was consistent with that of typical XSCID, and his Epstein-Barr virus-transformed B cells accordingly entirely lacked surface expression of c. On analysis by the reverse transcription-polymerase chain reaction (RT-PCR), a single but small c mRNA species was detected. Exon 6, which encodes the transmembrane domain of c, was skipped in the mRNA. A G to A mutation was found at the last nucleotide of exon 6 of the c gene (868GA). The predicted consequence of the exon skipping is a frameshift resulting in a premature stop codon, and the mutated c presumably loses association with the cell membrane. In XSCID, this mutation (868GA) is known as a missense mutation that results in Q285A. Previously reported patients with the same mutation apparently had no aberrant or alternative splicing but did have the Q285A exchange. Similar mutations at the last nucleotide of an outskipped exon have been reported. However, such mutations do not always cause exon skipping. Analyses of RNA structural changes induced by the mutations supported the variability of consequences of the mutations. Taken together, our findings suggest that the 868GA mutation of the c gene may affect c transcripts differently, i.e., generating missense or exon skipping, in XSCID patients with the same mutation. Patient-specific variation in splicing thus appears to occur.