Recurrent reciprocal genomic rearrangements of 17q12 are associated with renal disease, diabetes, and epilepsy

Am J Hum Genet. 2007 Nov;81(5):1057-69. doi: 10.1086/522591. Epub 2007 Sep 26.


Most studies of genomic disorders have focused on patients with cognitive disability and/or peripheral nervous system defects. In an effort to broaden the phenotypic spectrum of this disease model, we assessed 155 autopsy samples from fetuses with well-defined developmental pathologies in regions predisposed to recurrent rearrangement, by array-based comparative genomic hybridization. We found that 6% of fetal material showed evidence of microdeletion or microduplication, including three independent events that likely resulted from unequal crossing-over between segmental duplications. One of the microdeletions, identified in a fetus with multicystic dysplastic kidneys, encompasses the TCF2 gene on 17q12, previously shown to be mutated in maturity-onset diabetes, as well as in a subset of pediatric renal abnormalities. Fine-scale mapping of the breakpoints in different patient cohorts revealed a recurrent 1.5-Mb de novo deletion in individuals with phenotypes that ranged from congenital renal abnormalities to maturity-onset diabetes of the young type 5. We also identified the reciprocal duplication, which appears to be enriched in samples from patients with epilepsy. We describe the first example of a recurrent genomic disorder associated with diabetes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Autopsy
  • Chromosome Deletion
  • Chromosomes, Human, Pair 17 / genetics*
  • Diabetes Mellitus / genetics*
  • Epilepsy / complications
  • Epilepsy / genetics*
  • Female
  • Fetus / abnormalities
  • Gene Dosage
  • Gene Duplication
  • Gene Rearrangement / genetics*
  • Genetic Predisposition to Disease*
  • Genome, Human*
  • Humans
  • Kidney Diseases / complications
  • Kidney Diseases / genetics*
  • Male
  • Middle Aged
  • Nucleic Acid Hybridization
  • Pedigree
  • Phenotype