Maternal mosaicism for a novel interleukin-2 receptor gamma-chain mutation causing X-linked severe combined...

X-linked severe combined immunodeficiency disease (SCID) results from mutations of IL2RG, the gene encoding the interleukin-2 receptor gamma chain, also known as the common gamma chain (gamma c). A distinct form of autosomal recessive SCID occurs at an increased frequency among the Navajo Native American population. The disease gene responsible for autosomal Navajo SCID remains to be determined. We report the occurrence of X-linked SCID in a Navajo Native American kindred with two affected brothers. X-linked SCID was suggested by the presence of circulating B cells and the absence of surface gamma c expression in a cell line derived from an affected male. A C-to-T transition was demonstrated in exon 5 of the IL2RG gene, resulting in the substitution of tryptophan for arginine at position 224. This change was not present in the peripheral blood lymphocytes of the mother, thus proving the occurrence of a new mutation in the maternal germline. This report underscores the importance of establishing a specific genetic diagnosis for SCID cases and illustrates the inherent difficulties in providing genetic counseling in cases involving mosaicism.