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Molecular analysis of a constitutional complex genome rearrangement with 11 breakpoints involving chromosomes 3, 11, 12, and 21 and a ∼0.5-Mb submicroscopic deletion in a patient with mild mental retardation

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An Erratum to this article was published on 23 November 2005

Abstract

Complex chromosome rearrangements (CCRs) are extremely rare but often associated with mental retardation, congenital anomalies, or recurrent spontaneous abortions. We report a de novo apparently balanced CCR involving chromosomes 3 and 12 and a two-way translocation between chromosomes 11 and 21 in a woman with mild intellectual disability, obesity, coarse facies, and apparent synophrys without other distinctive dysmorphia or congenital anomalies. Molecular analysis of breakpoints using fluorescence in situ hybridization (FISH) with region-specific BAC clones revealed a more complex character for the CCR. The rearrangement is a result of nine breaks and involves reciprocal translocation of terminal chromosome fragments 3p24.1→pter and 12q23.1→qter, insertion of four fragments of the long arm of chromosome 12: q14.1→q21?, q21?→q22, q22→q23.1, and q23.1→q23.1 and a region 3p22.3→p24.1 into chromosome 3q26.31. In addition, we detected a ∼0.5-Mb submicroscopic deletion at 3q26.31. The deletion involves the chromosome region that has been previously associated with Cornelia de Lange syndrome (CdLS) in which a novel gene NAALADL2 has been mapped recently. Other potential genes responsible for intellectual deficiency disrupted as a result of patient’s chromosomal rearrangement map at 12q14.1 (TAFA2), 12q23.1 (METAP2), and 11p14.1 (BDNF).

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Acknowledgements

We gratefully acknowledge the Wellcome Trust Sanger Institute for providing BAC clones. This research was financed by the Polish Ministry of Scientific Research and Information Technology—Grant PBZ/KBN no. 042/P05/2001, the National Institute of Child Health and Development (PO1 HD39420), and the Baylor College of Medicine Mental Retardation Research Center (HD24064).

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Authors and Affiliations

  1. Department of Medical Genetics, Institute of Mother and Child, Kasprzaka 17A, 01-211, Warsaw, Poland

    Katarzyna Borg, Ewa Bocian, Ewa Obersztyn & Tadeusz Mazurczak

  2. Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX, USA

    Paweł Stankiewicz & James R. Lupski

  3. Department of Medical Genetics, Polish-American Children’s Hospital, Collegium Medicum, Jagiellonian University, Krakow, Poland

    Anna Kruczek

  4. Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA

    James R. Lupski

  5. Texas Children’s Hospital, Houston, TX, USA

    James R. Lupski

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  1. Katarzyna Borg
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  2. Paweł Stankiewicz
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  3. Ewa Bocian
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Correspondence to Tadeusz Mazurczak.

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An erratum to this article can be found at http://dx.doi.org/10.1007/s00439-005-0089-6

Appendix

Appendix

Table 1 The list of BAC clones used for mapping of breakpoints in the complex t(3;12) and the simple t(11;21) rearrangements. Clones spanning breakpoints and a deletion are marked with bold letters
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Borg, K., Stankiewicz, P., Bocian, E. et al. Molecular analysis of a constitutional complex genome rearrangement with 11 breakpoints involving chromosomes 3, 11, 12, and 21 and a ∼0.5-Mb submicroscopic deletion in a patient with mild mental retardation. Hum Genet 118, 267–275 (2005). https://doi.org/10.1007/s00439-005-0021-0

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