The Recurrent t(11;22)(q23;q11.2) Can Occur as a Post-Zygotic Event

• Published in: Cytogenetic and genome research Vol. 156; no. 4; p. 185
• Main Authors: Correll-Tash, Sarah, Conlin, Laura, Mininger, Beth A, Lilley, Brenna, Mennuti, Michael T, Emanuel, Beverly S
• Format: Journal Article
• Language: English
• Published: Switzerland 01-01-2018
• Subjects: Abortion, Spontaneous - genetics; Adult; Chromosomes, Human, Pair 11 - genetics; Chromosomes, Human, Pair 22 - genetics; Female; Humans; Karyotype; Mosaicism; Polycystic Ovary Syndrome - genetics; Sequence Analysis, DNA; Translocation, Genetic; Constitutional translocation; Emanuel syndrome; Somatic mosaicism; Meiotic malsegregation
• ISSN: 1424-859X
• DOI: 10.1159/000494648

The AT-rich repeat on chromosome 22q11.2 is known to be involved in the recurrent constitutional t(11;22)(q23;q11.2). Segregation of this translocation has been reported in several hundred families, but a de novo translocation event has been identified in only 8 cases, and everytime the translocation originated in paternal germ-line chromosomes. Further, de novo t(11;22) rearrangements have been detected in the sperm of healthy males, leading to the hypothesis that it occurs somewhere along the meiosis-spermatogenesis pathway. This report describes a woman whose constitutional karyotype revealed mosaicism for the recurrent t(11;22) and the subsequent testing performed to determine the origin of the translocation event. Karyotype analysis, translocation-specific PCR, human identity testing, and a SNP genotyping array were performed to detect mosaicism and/or chimerism. As a result, the SNP genotyping array revealed no evidence for mosaicism in genomic DNA beyond mosaicism for the balanced t(11;22). Human identity testing and the SNP genotyping array ruled out chimerism. PCR of the translocation breakpoint followed by sequencing confirmed that the translocation had occurred at the typical t(11;22) breakpoints. In conclusion, these results indicate that the translocation occurred post-fertilization, providing the first evidence of a de novo t(11;22)(q23;q11.2) occurring in a maternal mitotic environment.