2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-An Unusual Recombinant Chromosome 6 Derived from a Parental Double Paracentric Inversion

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Researchers report an unusual recombinant chromosome 6 derived from a parental double paracentric inversion. The study involved a family with various chromosomal rearrangements and genetic abnormalities. Chromosomal microarray analysis was performed on the tested individuals to assess copy number changes. Chromosome analysis and fluorescence in-situ hybridization (FISH) were used to clarify the nature of the structural rearrangements. Additionally, the short tandem repeat marker (STR) SE33 at 6q14 was analyzed to investigate the underlying mechanisms for recombinant formation.<br /><br />The study identified a 3-year-old male with multiple developmental delays and genetic abnormalities, including a deletion in the 6q22.31 region and a duplication in the 6q25.2-6q25.3 region. The same copy number changes were found in his brother and paternal half aunts, suggesting a complex structural abnormality caused by recombination of the double paracentric inversion.<br /><br />Chromosomal inversions are structural variations created by breaks and re-ligation of DNA segments. Paracentric inversions occur when breaks happen in one chromosome arm, while pericentric inversions occur when breaks occur in both arms of the chromosome. Carriers of inversions are usually not affected but have an increased risk of producing unbalanced gametes.<br /><br />The STR analysis provided insights into the mechanisms that produced different unbalanced recombinant chromosomes in the family. The study concluded that seemingly simple copy number changes on the same chromosome arm may represent a complex recombinant chromosome. Complex structural abnormalities resulting from recombination in carriers of double paracentric inversions may be rare but should be considered in patients with multiple copy number changes on the same chromosome arm.<br /><br />Overall, this study highlights the impact of chromosomal inversions and recombination on genetic abnormalities and the importance of comprehensive diagnostic workup in patients with complex structural abnormalities.

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Presenting Author - Melanie Babcock, PhD; Co-Author - Emily Lancaster, MS, CGC; Co-Author - Damara Ortiz, MD, FAAP, FACMG; Co-Author - Daniel B. Bellissimo, PhD; Co-Author - Evan Powell, BS; Co-Author - Svetlana A. Yatsenko, MD;

Meta Tag

array CGH

Chromosomal Abnormalities

Chromosome Structure/Function

Clinical Cytogenetics

Cytogenetics

FISH

Genetic Testing

Microarray

Molecular Cytogenetics

Co-Author Emily Lancaster, MS, CGC

Co-Author Damara Ortiz, MD, FAAP, FACMG

Co-Author Daniel B. Bellissimo, PhD

Co-Author Evan Powell, BS

Co-Author Svetlana A. Yatsenko, MD

Presenting Author Melanie Babcock, PhD

Keywords

recombinant chromosome 6

double paracentric inversion

chromosomal rearrangements

genetic abnormalities

chromosomal microarray analysis

copy number changes

chromosome analysis

fluorescence in-situ hybridization

short tandem repeat marker

structural variations