Discovery of the gene makes the direct molecular genetic diagnosis of Martin-Bell syndrome possible]

FORMULATION OF QUESTION: In 1991 four independent groups of geneticists succeeded in replacing the comparatively unreliable cytogenetic and indirect molecular diagnostics of the X-linked Martin-Bell-syndrome (MBS) by a more accurate approach. METHODS AND RESULTS: Fine structure analysis of the disease locus at Xq 27.3 led to the discovery of the fragile X mental retardation gene I (FMR I-gene), the mutative changes of which are responsible for the disease and can easily be detected in Southern hybridizations with gene probes out of this area. The observed changes are strong amplification of a repetitive CGG-motive in exon I of the gene in patients, a more moderate one in symptom-free carriers of the disease and changes in the promotor region of the gene to a varying extent in patients and carriers. CONCLUSION: This direct molecular diagnosis of MBS enables a safe identification of patients and carriers of the disease. A combined analysis of the observed mutations makes possible prenatal diagnosis, discriminating between carriers with and without symptoms. Especially this is necessary, since 20% of male and 50 to 70% of female mutation carriers are phenotypically normal.