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.
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).
Borg
Katarzyna
K
Department of Medical Genetics, Institute of Mother and Child, Kasprzaka 17A, 01-211, Warsaw, Poland.
Stankiewicz
Paweł
P
Bocian
Ewa
E
Kruczek
Anna
A
Obersztyn
Ewa
E
Lupski
James R
JR
Mazurczak
Tadeusz
T
D000328:Adult; D019457:Chromosome Breakage / Q000235:genetics*; D025063:Chromosome Disorders / Q000235:genetics* / Q000473:pathology; D002874:Chromosome Mapping / Q000379:methods; D002877:Chromosomes, Human / Q000235:genetics*; D000013:Congenital Abnormalities / Q000235:genetics / Q000473:pathology; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008607:Intellectual Disability / Q000235:genetics* / Q000473:pathology; D014178:Translocation, Genetic / Q000235:genetics*