Prenatal diagnosis of JAK3 deficient SCID

The JAK3 gene, encoding a tyrosine kinase functionally coupled to cytokine receptors which share the common gamma chain, has been identified as the de fective gene for autosomal recessive severe combined immunodeficiency (SCID ). Thus, specific mutational diagnosis has become possible. We screened all exons with a combined single strand conformational polymorphism and hetero -duplex formation assay followed by sequence analysis to identify specific mutations in two families. This assay was used on chorionic villus sampling derived DNA in two fetuses from two unrelated families, where we found mut ations in both parents. We were able to exclude the mutations in both fetus es by the 12th week of gestation. The described method for first-trimester prenatal diagnosis of autosomal recessive T-B+SCID provides a valid tool to aid in genetic counselling and possibly prenatal therapy in this disease. Copyright (C) 1999 John Wiley & Sons, Ltd.