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This Article Free to Access Full Text Full Text (PDF) web only tables All Versions of this Article: jmg.2007.052787v1 jmg.2007.052787v2 jmg.2007.052787v3 jmg.2007.052787v4 44/12/750    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this link to a friend Similar articles in this journal Similar articles in PubMed Add article to my folders Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by De Gregori, M Articles by Zuffardi, O Search for Related Content PubMed PubMed Citation Articles by De Gregori, M Articles by Zuffardi, O Topic Collections Unlocked

Cryptic deletions are a common finding in "balanced" reciprocal and complex chromosome rearrangements: a study of 59 patients

¹ Biologia Generale e Genetica Medica, Universitè di Pavia, Pavia, Italy
² IRCSS Policlinico San Matteo, Pavia, Italy
³ IRCCS E. Medea, Bosisio Parini, Lecco, Italy
⁴ Pediatria, Universitè di Siena, Siena, Italy
⁵ Dipartimento di Scienze Pediatriche, Universita’ di Torino, Torino, Italy
⁶ IRCCS C. Mondino, Universitè di Pavia, Pavia
⁷ Servizio di Citogenetica ASL-NA1, Napoli, Italy
⁸ Azienda Ospedaliera di Venere-Giovanni XXIII, Bari, Italy;
⁹ Dipartimento di Medicina Legale e Sanitè Pubblica, Universitè di Pavia, Pavia, Italy
¹⁰ Consultorio Genetico, Trento, Italy
¹¹ Citogenetica, Ospedale di Ravenna, Ravenna, Italy
¹² Genetica Medica, Universitè di Chieti, Chieti, Italy
¹³ Patologia Genetica e Prenatale, Policlinico G.B. Rossi, Verona, Italy
¹⁴ Institute of Medical Genetics, University of Zurich, Zurich, Switzerland
¹⁵ Dip. di Genetica e Microbiologia, Universitè di Bari, Bari, Italy
¹⁶ Fondazione Ospedale Maggiore, Mangiagalli e Regina Elena, Milano, Italy
¹⁷ Servizio Genetica Medica, Casa Sollievo della Sofferenza, San Giovanni rotondo, Italy
¹⁸ Oasi Institute for Research on Mental Retardation and Brain Aging, Troina, Italy
¹⁹ Genetica Medica, Universitè di Catania, Catania, Italy
²⁰ Ospedale San Raffaele, Milano, Italy
²¹ Istituto di Genetica Medica, Policlinico A. Gemelli, UCSC, Roma, Italy
²² Ospedale Pediatrico Meyer, Firenze, Italy
²³ Azienda Ospedaliera G. Rummo, Benevento, Italy
²⁴ 24 Genetica Medica, Ospedale San Bassiano, Bassano del Grappa, Italy
²⁵ Genetica Medica, Universitè di Ferrara, Ferrara, Italy
²⁶ Agilent Technologies, Santa Clara, California, USA
²⁷ Center for Human Genetics, University Hospital Gasthuisberg, Leuven, Belgium

Correspondence to:
O Zuffardi, Dipartimento di Patologia Umana ed Ereditaria, Sezione Biologia Generale e Genetica Medica, via forlanini 14, 27100 Pavia; zuffardi{at}unipv.it]

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.

Abbreviations: BAC, bacterial artificial chromosome; CCR, complex chromosome rearrangement; CGH, comparative genome hybridisation; DMD, Duchenne muscular dystrophy; DSB, double-strand break; FISH, flurorescence in situ hybridisation; PATRR, aplindromic AT-rich repeat; STR, short tandem repeat

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