Molecular characterization of the Pericentric Inversion breakpoints on X Chromosome in a Hypohidrotic Ectodermal Dysplasia patient with Mental Retardation

Abstract

Objectives: To characterize both X inversion breakpoints in a hypohidrotic ectodermal dysplasia patient with mental retardation in order to explain whether the Xp breakpoint can cause mental retardation and how the genotype, chromosomal inversion, causes the phenotype hypohidrotic ectodermal dysplasia. Materials and methods: Fluorescence in situ hybridization using BAC clones as probes was performed to determine precise breakpoints and to exclude the involvement of previously identified X-linked mental retardation genes. Polymerase chain reaction was used to further refine the breakpoints. Real-time polymerase chain reaction was carried out to quantitate gene expression. Results: FISH analysis documented that the Xp breakpoint did not disrupt any known X-linked mental retardation genes. The PCR results suggested that both breakpoints located within the repetitive sequences, with the Xq13 inversion breakpoint localized in the intron 3 of the EDA gene. Analysis of the transcripts of FAM51A1 gene flanking the breakpoint at Xp22.2 revealed that the inversion did not alter the expression of the gene. Conclusion: The inversion breakpoints on X chromosome disrupted the EDA gene which resulted in the clinical phenotypes of ectodermal dysplasia in this patient but did not disrupt any X-linked mental retardation genes and did not alter the expression of the nearby gene. The results suggested that mental retardation in this patient might not be caused by chromosome rearrangement.