Array-CGH fine mapping of minor and cryptic HR-CGH detected genomic imbalances in 80 out of 590 patients with abnormal development.
During a 6-year period, 590 patients suspected of having a minor or cryptic genomic imbalance as the cause of mental retardation with dysmorphic signs +/- malformations have been investigated with high-resolution comparative genomic hybridisation (HR-CGH) in our diagnostic laboratory. Thirty-six patients had a small chromosomal aberration detected by routine karyotyping, and 554 patients had a normal G-banded karyotype. In the latter group, a genomic imbalance was detected by HR-CGH in 40 patients (7.2%): 29 deletions, 3 duplications, 4 unbalanced translocations, and 4 occult trisomy mosaicisms. When microarray-based comparative genomic hybridisation (array-CGH) became available, all HR-CGH-positive samples were also investigated by 1 Mb resolution array-CGH for more precise mapping. From the 514 patients with normal HR-CGH findings, a subset of 20 patients with particularly high suspicion of having a chromosomal imbalance was selected for array-CGH. In four of them (20%), an imbalance was detected: three deletions and one duplication. Of note, 73 out of the 80 array-CGH mapped patients had a de novo chromosomal rearrangement (91%). Taken together, this work provides phenotype-genotype information on 80 patients with minor and cryptic chromosomal imbalances.
Lybaek
Helle
H
Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Helse Bergen HF, Bergen, Norway. helle.lybak@helse-bergen.no
Meza-Zepeda
Leonardo A
LA
Kresse
Stine H
SH
Høysaeter
Trude
T
Steen
Vidar M
VM
Houge
Gunnar
G
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002877:Chromosomes, Human / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D042822:Genomic Instability; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009693:Nucleic Acid Hybridization / Q000379:methods