Molecular cytogenetic analysis by genomic hybridization to determine the cause of recurrent miscarriage

• Published in: Fertility and sterility Vol. 93; no. 6; pp. 2075.e3 - 2075.e6
• Main Authors: Perrin, Aurore, Ph.D, Delobel, Bruno, M.D, Andrieux, Joris, M.D., Ph.D, Gosset, Philippe, M.D, Gueganic, Nadia, B.Sc, Petit, Florence, M.D, De Braekeleer, Marc, M.D., Ph.D, Morel, Frédéric, Ph.D
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2010
• Subjects: Abortion, Habitual - diagnosis; Abortion, Habitual - etiology; Abortion, Habitual - genetics; Adult; array-CGH; Comparative Genomic Hybridization; Cytogenetic Analysis; Female; Humans; Internal Medicine; Lymphocytes - cytology; Lymphocytes - metabolism; Male; meiotic segregation; Microdeletion; Obstetrics and Gynecology; Oligonucleotide Array Sequence Analysis; Pedigree; recurrent miscarriage; translocation; Microdeletion; recurrent miscarriage; translocation; meiotic segregation; array-CGH
• ISSN: 0015-0282; 1556-5653
• DOI: 10.1016/j.fertnstert.2009.11.016

Objective To characterize a t(2;6) by array-based comparative genomic hybridization (array-CGH) in a couple with recurrent miscarriage, to analyze the meiotic segregation of the t(2;6), and to discuss couple specific care-taking modality before intracytoplasmic sperm injection. Design Case report. Setting INSERM U613 in Brest, France. Patient(s) Couple consulting for infertility. Intervention(s) Array-CGH to characterize a t(2;6) and fluorescence in situ hybridization (FISH) to analyze the meiotic segregation were performed. Main Outcome Measure(s) Array-CGH, FISH with a panel of bacterial artificial chromosome clones and commercial probes. Result(s) Analyses from peripheral blood lymphocytes identified a t(2;6)(q35;q24) unbalanced reciprocal translocation with microdeletions on the der(2) and the der(6). FISH on spermatozoa found that the frequency of normal (23,X or 23,Y) or “translocation-deletions” (23,X,der(2),der(6) or 23,Y,der(2),der(6)) spermatozoa was 41.10%. Conclusion(s) For our 46,XY,t(2;6)(q35;q24) carrier, more than 50% of the spermatozoa are chromosomally unbalanced. Moreover, FISH does not permit a distinction between normal and “translocation-deletion” phenotypes. So, in the possibility of preimplantation genetic diagnosis, is it necessary to select the normal embryos to the detriment of those translocation-deletions carriers? The pathogenicity of these microdeletions not been proved. Because the family history was oriented toward a variation of genetic equipment without phenotypic consequences, the couple decided not to make a selection between the normal embryos and the translocation-deletion carrier embryos.