Human Genetics

, Volume 118, Issue 2, pp 267–275

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

  • Katarzyna Borg
  • Paweł Stankiewicz
  • Ewa Bocian
  • Anna Kruczek
  • Ewa Obersztyn
  • James R. Lupski
  • Tadeusz Mazurczak
Review Article


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).


Complex chromosomal rearrangement (CCR) Mapping of breakpoints Cryptic deletion Fluorescence in situ hybridization (FISH) 


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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Katarzyna Borg
    • 1
  • Paweł Stankiewicz
    • 2
  • Ewa Bocian
    • 1
  • Anna Kruczek
    • 3
  • Ewa Obersztyn
    • 1
  • James R. Lupski
    • 2
    • 4
    • 5
  • Tadeusz Mazurczak
    • 1
  1. 1.Department of Medical GeneticsInstitute of Mother and ChildWarsawPoland
  2. 2.Department of Molecular & Human GeneticsBaylor College of MedicineHoustonUSA
  3. 3.Department of Medical Genetics, Polish-American Children’s Hospital, Collegium MedicumJagiellonian UniversityKrakowPoland
  4. 4.Department of PediatricsBaylor College of MedicineHoustonUSA
  5. 5.Texas Children’s HospitalHoustonUSA

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