MATERNAL MOSAICISM FOR A NOVEL INTERLEUKIN-2 RECEPTOR GAMMA-CHAIN MUTATION CAUSING X-LINKED SEVERE COMBINED IMMUNODEFICIENCY IN A NAVAJO KINDRED

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 fo rm of autosomal recessive SCID, occurs at an increased frequency among the Navajo Native American population. The disease gene responsible f or autosomal Navajo SCID remains to be determined. We report the occur rence of X-linked SCID in a Navajo Native American kindred with two af fected brothers. X-linked SCID was suggested by the presce ence of cir culating B cells and the absence of surface gamma(c) expression in a c ell line derived from an affected male. A C-to-T transition was demons trated in exon 5 of the IL2RG gene, resulting in the substitution of t ryptophan for arginine at position 224. This change was not present in the peripheral blood lymphocytes of the mother, thus proving the occu rrence of a new mutation in the maternal germline. This report undersc ores the importance of establishing a specific genetic diagnosis for S CID cases and illustrates the inherent difficulties in providing genet ic counseling in cases involving mosaicism.