Definition of a critical region on chromosome 18 for congenital aural atresia by arrayCGH

Am J Hum Genet. 2003 Jun;72(6):1578-84. doi: 10.1086/375695. Epub 2003 May 9.


Deletions of the long arm of chromosome 18 occur in approximately 1 in 10,000 live births. Congenital aural atresia (CAA), or narrow external auditory canals, occurs in approximately 66% of all patients who have a terminal deletion 18q. The present report describes a series of 20 patients with CAA, of whom 18 had microscopically visible 18q deletions. The extent and nature of the chromosome-18 deletions were studied in detail by array-based comparative genomic hybridization (arrayCGH). High-resolution chromosome-18 profiles were obtained for all patients, and a critical region of 5 Mb that was deleted in all patients with CAA could be defined on 18q22.3-18q23. Therefore, this region can be considered as a candidate region for aural atresia. The array-based high-resolution copy-number screening enabled a refined cytogenetic diagnosis in 12 patients. Our approach appeared to be applicable to the detection of genetic mosaicisms and, in particular, to a detailed delineation of ring chromosomes. This study clearly demonstrates the power of the arrayCGH technology in high-resolution molecular karyotyping. Deletion and amplification mapping can now be performed at the submicroscopic level and will allow high-throughput definition of genomic regions harboring disease genes.

Publication types

  • Comparative Study

MeSH terms

  • Chromosome Banding
  • Chromosome Deletion
  • Chromosomes, Human, Pair 18*
  • Ear Canal / abnormalities*
  • Ear, External / abnormalities
  • Female
  • Gene Deletion
  • Humans
  • In Situ Hybridization, Fluorescence
  • Karyotyping
  • Nucleic Acid Hybridization / methods*
  • Ring Chromosomes
  • Translocation, Genetic