Application of molecular cytogenetic techniques to clarify apparently balanced complex chromosomal rearrangements in two patients with an abnormal phenotype: case report.
BACKGROUND
Complex chromosomal rearrangements (CCR) are rare cytogenetic findings that are difficult to karyotype by conventional cytogenetic analysis partially because of the relative low resolution of this technique. High resolution genotyping is necessary in order to identify cryptic imbalances, for instance near the multiple breakpoints, to explain the abnormal phenotype in these patients. We applied several molecular techniques to elucidate the complexity of the CCRs of two adult patients with abnormal phenotypes.


RESULTS
Multicolour fluorescence in situ hybridization (M-FISH) showed that in patient 1 the chromosomes 1, 10, 15 and 18 were involved in the rearrangement whereas for patient 2 the chromosomes 5, 9, 11 and 13 were involved. A 250 k Nsp1 SNP-array analysis uncovered a deletion in chromosome region 10p13 for patient 1, harbouring 17 genes, while patient 2 showed no pathogenic gains or losses. Additional FISH analysis with locus specific BAC-probes was performed, leading to the identification of cryptic interstitial structural rearrangements in both patients.


CONCLUSIONS
Application of M-FISH and SNP-array analysis to apparently balanced CCRs is useful to delineate the complex chromosomal rearrangement in detail. However, it does not always identify cryptic imbalances as an explanation for the abnormal phenotype in patients with a CCR.
de Vree
Paula Jp
PJ
Department of Clinical Genetics, Erasmus MC, Rotterdam, the Netherlands. p.j.poddighe@erasmusmc.nl.
Simon
Marleen Eh
ME
van Dooren
Marieke F
MF
Stoevelaar
Gerda Ht
GH
Hilkmann
José Tw
JT
Rongen
Michel A
MA
Huijbregts
Gido Cm
GC
Verkerk
Annemieke Jmh
AJ
Poddighe
Pino J
PJ