Divergence in cytogenetic and molecular genetic analysis results: a case report of Fragile X Syndrome among siblings.

Background: Fragile X Syndrome (FXS) is the most prevalent inherited cause of mental retardation. The prevalence of FXS in males and females are approximately 1 in 4000 and 1 in 8000 respectively. It is caused by CGG repeat instability in the FMR1 gene, located on chromosome Xq27.3. Normal individuals have CGG repeats ranging from 5 to 53. In premutation carriers, the CGG repeats range from 60 to 200 and shall be more than 200 repeats for full mutation patients. FXS patients have variable clinical features and because of that, an accurate clinical diagnosis is always a problem. Currently, Cytogenetic, PCR and Southern Blot Techniques are widely used for diagnosis of FXS. Case Report: Here we report a pair of brothers suspected to be FXS patients with similar clinical features. Peripheral blood was collected from both brothers and was subjected to cytogenetics and molecular analysis involving PCR, Southern blot and methylation specific PCR (MSPCR) analysis. However, the Cytogenetic result for the younger brother did not show the fragile site at Xq27.3 of the X chromosome while the molecular result was confirmatory for full mutation of FXS. Conversely, the elder brother showed confirmatory results for FXS in both Cytogenetic and molecular analysis. However, the result showed a mosaic pattern (full mutation and pre mutation FMR1 allele) which was confirmed by Southern blot and MSPCR analysis. Conclusion: We therefore conclude that elder brother confirms for Fragile X mosaic and younger brother for Fragile X full mutation. From the result, Cytogenetic analysis alone cannot be dependable for the confirmatory diagnosis of FXS. [ABSTRACT FROM AUTHOR]