Definition of a critical region on chromosome 18 for congenital aural atresia by arrayCGH.
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.
Veltman
Joris A
JA
Department of Human Genetics, University Medical Center Nijmegen, Nijmegen, The Netherlands. j.veltman@antrg.umcn.nl
Jonkers
Yvonne
Y
Nuijten
Inge
I
Janssen
Irene
I
van der Vliet
Walter
W
Huys
Erik
E
Vermeesch
Joris
J
Van Buggenhout
Griet
G
Fryns
Jean-Pierre
JP
Admiraal
Ronald
R
Terhal
Paulien
P
Lacombe
Didier
D
van Kessel
Ad Geurts
AG
Smeets
Dominique
D
Schoenmakers
Eric F P M
EF
van Ravenswaaij-Arts
Conny M
CM
D002871:Chromosome Banding; D002872:Chromosome Deletion; D002887:Chromosomes, Human, Pair 18; D004424:Ear Canal / Q000002:abnormalities*; D004431:Ear, External / Q000002:abnormalities; D005260:Female; D017353:Gene Deletion; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D009693:Nucleic Acid Hybridization / Q000379:methods*; D012303:Ring Chromosomes; D014178:Translocation, Genetic