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Original research
Recurring germline mosaicism in a family due to reversion of an inherited derivative chromosome 8 from an 8;21 translocation with interstitial telomeric sequences
  1. Weimin Bi1,2,
  2. Bo Yuan1,3,
  3. Pengfei Liu1,2,
  4. Jaclyn B Murry2,4,
  5. Xiang Qin3,
  6. Fan Xia1,2,
  7. Thao Quach2,
  8. Lance M Cooper2,
  9. Joanna Wiszniewska1,5,
  10. Patricia Hixson2,
  11. Sandra Peacock1,2,
  12. Vijay S Tonk6,
  13. Robert W Huff7,
  14. Veronica Ortega8,
  15. James R Lupski1,3,9,10,
  16. Steven E Scherer3,
  17. Rebecca Okashah Littlejohn11,
  18. Gopalrao V N Velagaleti8,
  19. Elizabeth R Roeder11,
  20. Sau Wai Cheung1
  1. 1Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
  2. 2Baylor Genetics, Houston, Texas, USA
  3. 3Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA
  4. 4Department of Pathology, The Johns Hopkins Hospital, Baltimore, Maryland, USA
  5. 5Department of Pathology and Laboratory Medicine, Oregon Health and Science University, Portland, Oregon, USA
  6. 6Departments of Pediatrics, Obstetrics and Gynecology, Pathology, Texas Tech University Health Science Centers, Lubbock, Texas, USA
  7. 7Department of Obstetrics and Gynecology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
  8. 8Department of Pathology and Laboratory Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
  9. 9Texas Children's Hospital, Houston, Texas, USA
  10. 10Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
  11. 11Department of Pediatrics and Molecular and Human Genetics, Baylor College of Medicine, San Antonio, Texas, USA
  1. Correspondence to Dr Sau Wai Cheung, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA; scheung{at}; Dr Elizabeth R Roeder; Elizabeth.roeder{at}


Background Mosaicism for chromosomal structural abnormalities, other than marker or ring chromosomes, is rarely inherited.

Methods We performed cytogenetics studies and breakpoint analyses on a family with transmission of mosaicism for a derivative chromosome 8 (der(8)), resulting from an unbalanced translocation between the long arms of chromosomes 8 and 21 over three generations.

Results The proband and his maternal half-sister had mosaicism for a der(8) cell line leading to trisomy of the distal 21q, and both had Down syndrome phenotypic features. Mosaicism for a cell line with the der(8) and a normal cell line was also detected in a maternal half-cousin. The der(8) was inherited from the maternal grandmother who had four abnormal cell lines containing the der(8), in addition to a normal cell line. One maternal half-aunt had the der(8) and an isodicentric chromosome 21 (idic(21)). Sequencing studies revealed microhomologies at the junctures of the der(8) and idic(21) in the half-aunt, suggesting a replicative mechanism in the rearrangement formation. Furthermore, interstitial telomeric sequences (ITS) were identified in the juncture between chromosomes 8 and 21 in the der(8).

Conclusion Mosaicism in the proband, his half-sister and half-cousin resulting from loss of chromosome 21 material from the der(8) appears to be a postzygotic event due to the genomic instability of ITS and associated with selective growth advantage of normal cells. The reversion of the inherited der(8) to a normal chromosome 8 in this family resembles revertant mosaicism of point mutations. We propose that ITS could mediate recurring revertant mosaicism for some constitutional chromosomal structural abnormalities.

  • Genomic Instability
  • Chromosome Aberrations
  • Genetic Phenomena
  • Cytogenetics
  • Human Genetics

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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  • ERR and SWC are joint senior authors.

  • Contributors The study was conceived and designed and responsible for the overall content as the guarantor by WB and SWC. WB contributed to acquisition of data, data analysis and interpretation, figure and table preparation, and drafting of the manuscript. JBM, TQ, LMC, JW and PH contributed to acquisition of data. BY, XQ, SES, and FX contributed to sequencing analysis of the breakpoints. PL and JRL contributed their expertise on breakpoint analysis and data interpretation. GVNV, VO, VST and RWH also contributed to acquisition of data and data interpretation. ROL and SP assisted in patient recruitment and sample collection. ERR contributed to providing clinical information, patient recruitment, sample collection, critical review of the manuscript. SWC contributed to data interpretation, overseeing project development and critical review of the manuscript. JRL, ROL, GVNV, VO, BY, PL, SP and JBM contributed significantly to manuscript revisions. All authors reviewed the manuscript and approved the final version. WB and SWC conceived and designed the studies and are responsible for the overall content as guarantors. ERR is responsible for the clinical data as guarantor.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.