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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #231449
Title: Prenatal detection and characterization of supernumerary marker chromosomes by array-CGH

Author
item SIMOVICH, M - BAYLOR COLLEGE MED
item KANG, SH - BAYLOR COLLEGE MED
item PATEL, A - BAYLOR COLLEGE MED
item PURSLEY, A - BAYLOR COLLEGE MED
item CHINAULT, A - BAYLOR COLLEGE MED
item LUPSKI, J - BAYLOR COLLEGE MED
item BEAUDET, A - BAYLOR COLLEGE MED
item Van Den Veyver, Ignatia
item CHEUNG, S - BAYLOR COLLEGE MED

Submitted to: American Society of Human Genetics
Publication Type: Abstract Only
Publication Acceptance Date: 10/23/2007
Publication Date: 10/23/2007
Citation: Simovich, M.J., Kang, S.H.L., Patel, A., Pursley, A., Chinault, A.C., Lupski, J.R., Beaudet, A.L., Van Den Veyver, I.B., Cheung, S.W. 2007. Prenatal detection and characterization of supernumerary marker chromosomes by array-CGH [abstract]. In: 57th Annual Meeting of The American Society of Human Genetics, October 23-27, 2007, San Diego, California. p. 458.

Interpretive Summary:

Technical Abstract: Small supernumerary marker chromosomes (sSMC) occur in about 0.043% of newborns and in 0.076% of prenatal diagnoses. The phenotypes associated with sSMC vary substantially depending on size, gene content, and chromosome origin, which cannot easily be determined by karyotype or FISH analysis. Therefore, prediction of the pregnancy outcome is difficult, and genetic counseling can be a challenge. We analyzed five prenatal cases referred to our laboratory for chromosome microarray analysis (CMA) by array-CGH after karyotype analysis showed an uncharacterized sSMC. In case 1, CMA detected a gain of DNA copy number in the pericentromeric region of 12q, estimated to be approximately 5Mb in size. Metaphase FISH analysis revealed a minute ring-like sSMC in 16 to 20 cells analyzed. In case 2, array-CGH detected a gain of approx. 4Mb on chromosome 12p. FISH analysis showed that the marker was present in 2.5% of the cells and corroborated the chromosome 12p origin. In case 3, array-CGH detected an 18 Mb gain in the proximal region of chromosome 21q that was confirmed by interphase FISH analysis on cultured amniocytes in 100% of the cells. Postnatal follow-up by array-CGH also confirmed the results. The sSMCs in case 4 and 5 were shown to have originated from the fusion of the centromeric heterochromatin of one or both chromosomes 14 and 22 by G banded chromosome and FISH analyses. The array-CGH did not detect any abnormalities. Since the array is designed to detect unique sequences in the pericentromeric regions, these results suggest there is no apparent genetically active chromatin material present in the marker. We show that the origin of sSMC cannot be identified by conventional cytogenetic analysis alone. Their precise characterization requires high resolution genome analyses by molecular techniques; of these, array-CGH emerges as the fastest and most precise diagnostic tool to determine the chromosomal origin and approximate size of the sSMC. This improved characterization, is crucial for accurate prenatal genetic counseling.