Molecular Diagnosis of Congenital Immunodeficiency

The congenital immunodeficiencies are a group of inherited conditions in which there are defects of immune function. The last decade has seen the identification of most of the genes defective in these disorders (1 ). Diagnostic genetic assays have been developed for many of these conditions so that a molecular diagnosis can be assigned to individuals and genetic testing offered for carrier status and antenatal diagnosis. Most genetic testing now involves screening the gene for the defective exon using one of a number of techniques, the most popular of which is single-stranded conformational polymorphism (SSCP) analysis (2 ). Once the affected region is identified, direct sequence analysis can be performed to identify the precise mutation. This procedure has a number of disadvantages. If a gene has many exons, screening the gene using SSCP can be time consuming, and in cases where the clinical picture is ambiguous or atypical, can result in diagnostic delay. The sensitivity of the SSCP technique is also only 85% and thus a number of affected cases may be left undiagnosed.