Identification of X-linked severe combined immunodeficiency by mutation analysis of blood and hair roots

Severe combined immunodeficiency is a heterogenous syndrome of varied genet ic origins of which the X-linked type is the commonest (XSCID). The most se nsitive method for diagnosis of XSCID in the absence of X-linked inheritanc e pattern is by mutation analysis. In this report we have performed mutation analysis in 13 unrelated bogs tra nsplanted (BMT) for SCID without a known cause to determine the frequency o f XSCID, Five boys had an affected male relative. We also assessed the util ity of hair roots for children without pre-transplant blood stored for muta tion analysis since donor genotype was expressed in peripheral blood post B MT. Screening was performed by analysis of single-strand conformational pol ymorphism (SSCP) followed by sequencing of candidate exons. Mutations were found in 11 cases, of which six were sporadic, and maternal mosaicism was found in one family, Three mothers of the six sporadic cases were identified as carriers. The majority (6/8) of boys with SCID had gamma c deficiency despite the absence of X-linked inheritance pattern. The sign ificant frequency of de novo mutations and the occurrence of maternal germl ine mosaicism highlights the importance of mutation analysis, The strategy of using DNA from hair roots was particularly valuable where no pretranspla nt blood was stored, Characterization of the mutations will also enable res earch into the correction of these genetic defects.