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

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.

Key Words: Microdeletion, array-CGH, meiotic segregation, recurrent miscarriage, translocation