Recurrent 8q13.2-13.3 microdeletions associated with Branchio-oto-renal syndrome are mediated by human endogenous retroviral (HERV) sequence blocks

Background: Human endogenous retroviral (HERV) sequences are the remnants of ancient retroviral infection and comprise approximately 8% of the human genome. The high abundance and interspersed nature of homologous HERV sequences make them ideal substrates for genomic rearrangements. A role for HERV sequences in mediating human disease-associated rearrangement has been reported but is likely currently underappreciated. Methods and Results: In the present study, two independent de novo 8q13.2-13.3 microdeletion events were identified in patients with clinical features of Branchio-Oto-Renal (BOR) syndrome. Nucleotide-level mapping demonstrated the identical breakpoints, suggesting a recurrent microdeletion including multiple genes such as EYA1, SULF1, and SLCO5A1, which is mediated by HERV1 homologous sequences. Conclusions: These findings raise the potential that HERV sequences may more commonly underlie recombination of dosage sensitive regions associated with recurrent syndromes.