Detection of submicroscopic chromosome abnormalities by comparative genomic hybridization

Background: The purpose was to detect chromosome abnormalities in dysmorphic and mentally retarded individuals with normal karyotypes by means of comparative genomic hybridisation (CGH).

Methods: One hundred and forty-four individuals with normal karyotype underwent CGH analysis with a new detection technique where fixed limits are replaced by dynamic standard reference intervals. This method provides improved resolution and thereby detects minor chromosome abnormalities.

Results: Fifteen minor abnormalities (10%) and one trisomy 9 mosaic were found. Eleven were interstitial deletions or duplications, which cannot be detected by screening with other cytogenetic techniques. Three were terminal deletions or duplications and one was a terminal unbalanced translocation.

Conclusions: CGH analysis with dynamic standard reference intervals is a new objective and quantitative method, which is suitable for screening for small chromosome abnormalities that can not be detected by conventional chromosome analysis. The method is recommended for use in the investigation of dysmorphic and mentally retarded individuals, in whom abnormalities are not found by ordinary karyotyping.