Prenatal diagnosis of a 9q34.3 microdeletion by array-CGH in a fetus with an apparently balanced translocation.
OBJECTIVE
Use high-resolution genome analysis to clarify the genomic integrity in a fetus with a cytogenetically balanced translocation t(2;9)(q11.2;q34.3).


METHODS
High resolution molecular cytogenetic analyses including G-banded chromosome analysis, fluorescence in situ hybridization (FISH), and array-comparative genomic hybridization (CGH) were performed on cultured cells, and DNA extracted from chorionic villus sample (CVS), amniotic fluid cells and fetal tissue. In addition, a custom fosmid-based tiling path 9q34.3 microarray with a resolution of 35-40 kb was used for array-CGH.


RESULTS
GTG-banding analysis showed an apparently balanced de novo translocation between the long arms of chromosomes 2 and 9; t(2;9)(q11.2;q34.3). Array-CGH using a targeted chromosomal microarray analysis (CMA) uncovered a submicroscopic deletion of the subtelomeric region of 9q34.3 revealing the unbalanced nature of the rearrangement. These results were confirmed independently by FISH. The deletion was delimited to 2.7 Mb in size using the 9q34.3 fosmid-based tiling path array-CGH.


CONCLUSIONS
Array-CGH is a powerful tool for rapid detection of genomic imbalances associated with microdeletion/duplication syndromes and for the evaluation of de novo apparently balanced translocation to enable high-resolution genomic analysis at the breakpoints. Prenatal diagnosis of chromosomal rearrangements involving dosage-sensitive genomic regions is an important adjuvant to prenatal care and provides more accurate information for counseling and informed decision making.
Simovich
Marcia J
MJ
Departments of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Yatsenko
Svetlana A
SA
Kang
Sung-Hae L
SH
Cheung
Sau Wai
SW
Dudek
Martha E
ME
Pursley
Amber
A
Ward
Patricia A
PA
Patel
Ankita
A
Lupski
James R
JR
D000328:Adult; D002872:Chromosome Deletion; D002899:Chromosomes, Human, Pair 9; D005260:Female; D005333:Fetus / Q000648:ultrastructure*; D006801:Humans; D009693:Nucleic Acid Hybridization / Q000379:methods*; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D014178:Translocation, Genetic