Trisomy 12 mosaicism confirmed in multiple organs from a liveborn child

Area of Science:

• Genetics
• Developmental Biology
• Human Pathology

Background:

• Mosaic aneuploidy, characterized by the presence of cell lines with an abnormal chromosome number, presents a diagnostic challenge.
• Pigmentary dysplasia is a non-specific but frequent indicator of chromosomal mosaicism.
• Understanding the origin and distribution of aneuploid cells is crucial for predicting phenotype severity.

Observation:

• A patient with trisomy 12 mosaicism confirmed in multiple organs exhibited pigmentary dysplasia and died in infancy due to complex heart malformation.
• Cytogenetic and interphase fluorescent in situ hybridization (FISH) analyses revealed highly variable aneuploid cell distribution across nine tissues, ranging from 0% in blood and ovary to 100% in spleen and liver.
• The trisomy was determined to have a meiotic origin, specifically maternal meiosis I, with subsequent post-zygotic loss of a chromosome 12.

Findings:

• This is the fifth postnatal diagnosis of trisomy 12 mosaicism and the first to pinpoint maternal meiosis I as the origin.
• Uniparental disomy for chromosome 12 in the diploid cell line was excluded.
• The severe phenotype, including early mortality and malformations, correlated with a high percentage of trisomic cells.

Implications:

• The variable distribution and proportion of aneuploid cells significantly influence the clinical presentation and severity of mosaic aneuploidy syndromes.
• This case highlights the importance of multi-tissue analysis in diagnosing and understanding chromosomal mosaicism.
• Further research into the timing of non-disjunctional errors can elucidate the mechanisms behind phenotypic variability in mosaic aneuploidies.