TY - JOUR T1 - Cryptic deletions are a common finding in “balanced” reciprocal and complex chromosome rearrangements: a study of 59 patients JF - Journal of Medical Genetics JO - J Med Genet SP - 750 LP - 762 DO - 10.1136/jmg.2007.052787 VL - 44 IS - 12 AU - M De Gregori AU - R Ciccone AU - P Magini AU - T Pramparo AU - S Gimelli AU - J Messa AU - F Novara AU - A Vetro AU - E Rossi AU - P Maraschio AU - M C Bonaglia AU - C Anichini AU - G B Ferrero AU - M Silengo AU - E Fazzi AU - A Zatterale AU - R Fischetto AU - C Previderé AU - S Belli AU - A Turci AU - G Calabrese AU - F Bernardi AU - E Meneghelli AU - M Riegel AU - M Rocchi AU - S Guerneri AU - F Lalatta AU - L Zelante AU - C Romano AU - M Fichera AU - T Mattina AU - G Arrigo AU - M Zollino AU - S Giglio AU - F Lonardo AU - A Bonfante AU - A Ferlini AU - F Cifuentes AU - H Van Esch AU - L Backx AU - A Schinzel AU - J R Vermeesch AU - O Zuffardi Y1 - 2007/12/01 UR - http://jmg.bmj.com/content/44/12/750.abstract N2 - Using array comparative genome hybridisation (CGH) 41 de novo reciprocal translocations and 18 de novo complex chromosome rearrangements (CCRs) were screened. All cases had been interpreted as “balanced” by conventional cytogenetics. In all, 27 cases of reciprocal translocations were detected in patients with an abnormal phenotype, and after array CGH analysis, 11 were found to be unbalanced. Thus 40% (11 of 27) of patients with a “chromosomal phenotype” and an apparently balanced translocation were in fact unbalanced, and 18% (5 of 27) of the reciprocal translocations were instead complex rearrangements with >3 breakpoints. Fourteen fetuses with de novo, apparently balanced translocations, all but two with normal ultrasound findings, were also analysed and all were found to be normal using array CGH. Thirteen CCRs were detected in patients with abnormal phenotypes, two in women who had experienced repeated spontaneous abortions and three in fetuses. Sixteen patients were found to have unbalanced mutations, with up to 4 deletions. These results suggest that genome-wide array CGH may be advisable in all carriers of “balanced” CCRs. The parental origin of the deletions was investigated in 5 reciprocal translocations and 11 CCRs; all were found to be paternal. Using customised platforms in seven cases of CCRs, the deletion breakpoints were narrowed down to regions of a few hundred base pairs in length. No susceptibility motifs were associated with the imbalances. These results show that the phenotypic abnormalities of apparently balanced de novo CCRs are mainly due to cryptic deletions and that spermatogenesis is more prone to generate multiple chaotic chromosome imbalances and reciprocal translocations than oogenesis. ER -