INTERSTITIAL DELETION OF CHROMOSOME 6Q - PRECISE DEFINITION OF THE BREAKPOINTS BY MICRODISSECTION DNA AMPLIFICATION, AND REVERSE PAINTING

Routine chromosomal analysis using GTG-banding alone showed a mosaic t erminal deletion of 6q in a 14-week-old boy with developmental retarda tion, facial anomalies, agenesis of corpus callosum, cleft palate, hyp otonia, short neck and pterygium colli, and minor anomalies of hands a nd feet. Discrepancies between the clinical findings on our patient an d those described in the literature on patients having terminal deleti ons led to a more precise analysis of the karyotype. Reverse painting was performed on normal G-banded metaphases for exact determination of the breakpoints and on metaphases of the patient for evaluation of mo saicism. A DNA library that was obtained by microdissection of three d eleted chromosomes 6 was used as a painting probe. Subsequent DNA ampl ification was performed with the help of topoisomerase-pretreated dege nerate oligonucleotide primers. Unexpectedly, the hybridization patter n on normal metaphase chromosomes revealed an interstitial deletion wi th breakpoints at 6q25.1 and 6q27 instead of a terminal deletion. Hybr idization on metaphases of the patient showed one deleted chromosome 6 in all metaphases analyzed at a higher resolution rather than mosaici sm as previously assumed [karyotype, 46,XY,del(6)(q25.1-->q27)]. We as sume that in the single cases of 6q described in the literature the de letions are misclassified. This might be due to difficulties in distin guishing between interstitial and terminal deletions at 6q and in prec isely defining chromosomal breakpoints after GTG-banding alone.