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Ring chromosome 21 in a boy and a derivative chromosome 21 in the mother: implication for ring chromosome formation
Koji Muroya1, Keiichi Yamamoto, Yoshimitsu Fukushima
1Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.
Insights
A novel U-type exchange mechanism is proposed for ring chromosome 21 (r(21)) formation. This process involves duplicated distal 21q regions on a derivative chromosome 21 (der(21)) in the mother, leading to r(21) in her son.
Area of Science:
- Cytogenetics
- Molecular Genetics
- Human Genetics
Background:
- Ring chromosomes are unstable and can lead to various genetic disorders.
- The formation of ring chromosomes, particularly ring chromosome 21 (r(21)), is not fully understood.
- Understanding r(21) formation is crucial for genetic counseling and diagnosis.
Observation:
- Cytogenetic analysis revealed a mosaic r(21) karyotype in a boy and a derivative chromosome 21 (der(21)) karyotype in his mother.
- Fluorescence in situ hybridization (FISH) and microsatellite analysis characterized the genetic content and structure of both r(21) and der(21) chromosomes.
- The r(21) chromosome lacked telomeric regions and a portion of 21q22.3, while the der(21) chromosome showed duplication and inversion of 21q22.1-21q22.2 and duplication of distal 21q22.3.
Findings:
- The study identified a novel U-type exchange mechanism as the likely cause of r(21) formation.
- This mechanism involves homologous recombination between duplicated distal 21q regions on the maternal der(21) chromosome.
- The findings suggest that the der(21) chromosome in the mother served as a substrate for the U-type exchange, leading to the r(21) in the son.
Implications:
- This discovery provides a new molecular mechanism for the formation of monocentric ring chromosomes.
- The findings enhance our understanding of chromosomal abnormalities and their inheritance patterns.
- This knowledge can aid in the genetic diagnosis and counseling of families with r(21).
Abstract:
We report on r(21) chromosome in a boy and a der(21) chromosome in his mother. Cytogenetic studies revealed a mosaic 45,XY[4]/46,XY,r(21)[96] karyotype in the boy and a 46,XX,der(21)[100] karyotype in the mother. Fluorescence in situ hybridization analysis for D21Z1 at the centromere, AML1 at 21q22.1, LSI21 at 21q22.2, and 21qtel at the telomere region showed that the r(21) chromosome retained single copies of D21Z1, AML1, and LSI21 and lacked the 21qtel, whereas the der(21) chromosome had two copies of the 21qtel on both of its ends and single copies of D21Z1, AML1, and LSI21, with a paracentric inversion of AML1 and LSI21 (21qtel-D21Z1-LSI21-AML1-21qtel). Microsatellite analysis for nine loci on 21q22.3 indicated that the r(21) chromosome was missing a distal 21q22.3 region involving D21S1890, D21S1411, and D21S1903 with no maternally derived alleles, and that the der(21) chromosome was associated with duplication of a distal 21q22.3 region encompassing D21S1890 and D21S1446. The results suggest that a U-type exchange occurred between the homologous distal 21q regions duplicated on the der(21) chromosome, leading to the r(21) formation. This is a novel mechanism put forward for the formation of a monocentric ring chromosome.