Mapping chromosome breakpoints using fiber-fish in a family with a translocation t(9;14)(q34;ql3) and psychiatric illness

We have studied a two generation Scottish family where a chromosome abnormality t(9;14)(q34;q13) of maternal origin, cosegregates with schizophrenia and/or learning disability. Transformed cell lines have been established on two translocation carriers, one with schizophrenia and mild learning disability and the other with schizophreniform psychosis and severe learning disability. The chromosome 14q break occurs in a cytogenetic region where familial cases of Fahr syndrome (idiopathic basal ganglia calcification) show significant linkage. Fahr syndrome is a clinically pleiomorphic condition where an estimated 50% of the affected cases are predisposed to a psychiatric disorder. The t(9;14) chromosome breakpoint junction was initially determined by mapping onto the aberrant flow sorted chromosomes. The breakpoint junction was confirmed by FISH mapping with selected CEPH YAC clones located at 14q13. Moreover, to further characterize the breakpoint junction, we used selected BAC clones as probes for fiberFISH onto extended DNA fibres to ascertain any additional rearrangements. The clinical variability observed in the affected mother and child could be due to intrasyndromic variability and/or instability at the breakpoint junction during meiosis leading to microdeletions in the germline of the affected mother. The availability of the human genomic sequence at the translocation breakpoint junction will provide putative candidate genes for this chromosomal case.