De novo t(7;10)(q33;q23) translocation and closely juxtaposed microdeletion in a patient with macrocephaly and developmental delay

We have applied FISH with fully integrated BACs and BAC subfragments assessed in the human genome sequence to a de novo t(7;10)(q33;q23) translocation in a patient with developmental delay and macrocephaly. The translocation breakpoints disrupt the SEC8L1 gene on chromosome 7 and the PTEN gene on chromosome 10. RT-PCR demonstrated chimeric transcripts containing the first 11 exons of SEC8L1 fused to exon 3 of PTEN. In addition to the balanced translocation, we found a 7-Mb deletion in the translocated part of chromosome 7 at 4-Mb distance of the translocation breakpoint. This microdeletion, which disrupts the PTN and TPK1 genes and deletes 29 bonafide genes and the T-cell receptor beta locus, arose in the paternal germline. The patient’s phenotype may be caused by a dominant-negative effect of the SEC8L1-PTEN fusion protein and/or haploinsufficiency of the disrupted or deleted genes. Our study demonstrates that de novo translocations can be associated with microdeletions outside the breakpoint region(s), rendering the study and risk estimation of such breakpoints more complicated than previously assumed.