Jornal de doenças genéticas e relatórios genéticos

A Rare Case of Isodicentric Xq28 that Causes Mental Retardation: Molecular Characterization and Review

Gonzalez  C, Gutierrez M,  Ruiz ML, Huete B, Gonzalez S, Gallego J and Cava F

Study background: Isodicentric X chromosome is a rare structural abnormality in which the arms of the chromosome are mirror images of each other with two centromeres. Little description is available about characterization or phenotype-genotype association in isodicentric Xq28. While some of the females are normal, most only present premature ovarian failure or amenorrhea, but mental retardation is not usually reported.

Methods: We present a study of cytogenetic and molecular characterization of an isodicentric Xq28 found in a development retarded girl with dysmorphic features. G and C banding, CGH array and Bisulfite Methylation techniques were used.

Results: The study showed an almost total trisomy of X chromosome (Xper->Xq28) with a 1.10 Mb deletion in Xq28:qter, with two centromeres and a total skewed inactivation of one X chromosome. The deletion in Xq28 in this patient includes genes that are implicated in X-linked mental retardation and autism spectrum disorder.

Conclusion: Molecular studies help to elucidate genes that are implicated to understand the phenotype. The mental retardation and dysmorphic features in our patient can be attributed to the affected genes, their regulation and tissue expression. Although mental retardation is not usually reported this possibility has to be taken into account inorder to suggest a genetic counselling in prenatal diagnosis and de novo findings. Literature on isodicentric X chromosomes with various breakpoints on Xq is reviewed and summarized in this report.