Breakpoint Mapping of Symptomatic Balanced Translocations Links the EPHA6 , KLF13 and UBR3 Genes to Novel Disease Phenotype.

De novo balanced chromosomal aberrations (BCAs), such as reciprocal translocations and inversions, are genomic aberrations that, in approximately 25% of cases, affect the human phenotype. Delineation of the exact structure of BCAs may provide a precise diagnosis and/or point to new disease loci. We report on six patients with de novo balanced chromosomal translocations (BCTs) and one patient with a de novo inversion, in whom we mapped breakpoints to a resolution of 1 bp, using shallow whole-genome mate pair sequencing. In all seven cases, a disruption of at least one gene was found. In two patients, the phenotypic impact of the disrupted genes is well known ( NFIA, ATP7A ). In five patients, the aberration damaged genes: PARD3, EPHA6, KLF13, STK24, UBR3, MLLT10 and TLE3 , whose influence on the human phenotype is poorly understood. In particular, our results suggest novel candidate genes for retinal degeneration with anophthalmia ( EPHA6 ), developmental delay with speech impairment ( KLF13 ), and developmental delay with brain dysembryoplastic neuroepithelial tumor ( UBR3 ). In conclusion, identification of the exact structure of symptomatic BCTs using next generation sequencing is a viable method for both diagnosis and finding novel disease candidate genes in humans.