Clinical and molecular cytogenetic characterization of two patients with non-mutational aberrations of the FMR2 gene.

We report on two patients; a female having mild mental retardation (MR) with a balanced translocation, 46,XX,t(X;15)(q28;p11.2), and a male diagnosed as having mucopolysaccharidosis type II (MPS II or Hunter syndrome) with atypical early-onset MR and a normal male karyotype. Molecular cytogenetic analyses, including fluorescence in situ hybridization and array-based comparative genomic hybridization using an in-house X-tiling array, revealed that first patient to have a breakpoint at Xq28 lying within the FMR2 gene and the second to have a small deletion at Xq28 including part of FMR2 together with the IDS gene responsible for MPS II. In Patient 1, X-chromosome inactivation predominantly occurred in the normal X in her lymphocytes, suggesting that her MR might be explained by a disruption of the FMR2 gene on der(X) t(X;15) concomitant with the predominant inactivation of the intact FMR2 gene in another allele. We compared phenotypes of Patient 2 with those of MPS II cases with deletion of the IDS gene alone reported previously, suggesting that the early-onset MR might be affected by the additional deletion of FMR2.