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

• Published in: Human genetics Vol. 118; no. 2; pp. 267 - 275
• Main Authors: Borg, Katarzyna, Stankiewicz, Paweł, Bocian, Ewa, Kruczek, Anna, Obersztyn, Ewa, Lupski, James R, Mazurczak, Tadeusz
• Format: Journal Article
• Language: English
• Published: Germany 01.11.2005
• Subjects: Adult; Chromosome Breakage - genetics; Chromosome Disorders - genetics; Chromosome Disorders - pathology; Chromosome Mapping - methods; Chromosomes, Human - genetics; Congenital Abnormalities - genetics; Congenital Abnormalities - pathology; Female; Humans; In Situ Hybridization, Fluorescence - methods; Intellectual Disability - genetics; Intellectual Disability - pathology; Translocation, Genetic - genetics
• ISSN: 0340-6717

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 approximately 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).