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

Area of Science:

• Genetics
• Human Genetics
• Reproductive Genetics

Background:

• The constitutional t(11;22) translocation is a recurrent genetic event associated with the AT-rich repeat on chromosome 22q11.2.
• While hundreds of families exhibit segregation of this translocation, de novo events are rare (8 cases) and have exclusively been linked to paternal germ-line origins.
• Previous findings of de novo t(11;22) in sperm suggested an occurrence during meiosis or spermatogenesis.

Observation:

• This study investigated a woman with constitutional karyotype mosaicism for the t(11;22) translocation.
• Advanced molecular techniques including karyotype analysis, translocation-specific PCR, human identity testing, and SNP genotyping array were employed.
• Testing aimed to detect mosaicism and/or chimerism to pinpoint the translocation's origin.

Findings:

• SNP genotyping revealed no mosaicism beyond the balanced t(11;22).
• Human identity testing and SNP array excluded chimerism.
• PCR and sequencing confirmed the translocation occurred at the canonical t(11;22) breakpoints.

Implications:

• The findings indicate that the de novo t(11;22) translocation occurred post-fertilization.
• This research presents the first evidence of a de novo t(11;22)(q23;q11.2) originating in a maternal mitotic environment.
• This challenges previous hypotheses and expands understanding of the origins of recurrent constitutional translocations.