Persistent mosaicism for 12p duplication/triplication chromosome structural abnormality in peripheral blood

Area of Science:

• Genetics
• Human Genetics
• Chromosomal Abnormalities

Background:

• Pallister-Killian syndrome is a rare genetic disorder characterized by specific phenotypic features.
• Mosaicism, the presence of two or more cell lines with different genotypes, can occur in chromosomal abnormalities.
• Isochromosome 12p, leading to tetrasomy 12p, is a common cause of Pallister-Killian syndrome.

Purpose of the Study:

• To describe a rare case of mosaicism for a structural abnormality of chromosome 12.
• To investigate the genetic basis and origin of the chromosomal abnormality.
• To analyze the clinical presentation in relation to the observed mosaicism.

Main Methods:

• Karyotyping to identify chromosomal abnormalities.
• Fluorescence in situ hybridization (FISH) to confirm duplication/triplication of 12p loci.
• Genome-wide single nucleotide polymorphism (SNP) array analysis to determine the origin of the duplication.

Main Results:

• A six-month-old patient presented with features of Pallister-Killian syndrome.
• Mosaicism was detected, with 25% of cells showing a normal karyotype and the remaining cells having a structural abnormality of chromosome 12 with 12p duplication/triplication.
• SNP array analysis indicated maternal origin of the duplicated/triplicated regions.
• The abnormal cell line persisted at 19 months, suggesting altered cell growth dynamics compared to typical tetrasomy 12p.

Conclusions:

• This case highlights rare mosaicism for a structural chromosome 12 abnormality presenting as Pallister-Killian syndrome.
• The maternal origin of the abnormality was established.
• The persistence of the abnormal cell line may indicate that genes causing growth disadvantage in tetrasomy 12p might have less impact in trisomy 12p.