Characterization of a de novo balanced translocation in a patient with moderate mental retardation and dysmorphic features.

ABSTRACT

Moderate mental retardation (MR) could affect up to 3% of the general population. A proportion of these cases has a genetic origin. Genes responsible for mental retardation can be identified taking advantage of familial cases or patients carrying a chromosomal rearrangement. We have studied a female patient with mild mental retardation and dysmorphic features. Cytogenetic and molecular investigations revealed a de novo balanced translocation 46, XX, t(5;18)(q21.3;q21.32) in the patient. The karyotypes of the parents are normal. We mapped the breakpoints of the translocation on chromosomes 5 and 18 by fluorescence in situ hybridization (FISH). The characterization of the chromosomal breakpoints helped us identify a new candidate region containing a portion of a gene. This gene is called FER. It is a tyrosine kinase located on the chromosome 5q21.3. We found no known genes in the genomic region corresponding to the BAC spanning the 18q21.32 breakpoint. Molecular analysis showed that the FER gene was not interrupted by the translocation breakpoint on chromosome 5. Real-time quantitative PCR performed using RNA from the patient, compared to her parents and controls, showed no significant modification of FER expression ruling out a putative position effect, at least in the tissue tested. Our data suggest that FER is not implicated in the mental retardation phenotype observed in the reported patient. Therefore the MR phenotype might not be caused by the translocation.