Birth of a child with trisomy 9 mosaicism syndrome associated with paternal isodisomy 9: case of a positive noninvasive prenatal test result unconfirmed by invasive prenatal diagnosis

Molecular Cytogenetics

Hong Pan²  Huixia Yang²  Ling Shang¹  Jianguang Zhang¹  David S. Cram¹  Jingmei Ma² 

[1] Berry Genomics, Building 9, No 6 Court Jingshun East Road, Chaoyang District, Beijing 100015, China;Department of Obstetrics, Peking University First Hospital, No.1 Xianmen Street, Xicheng District, Beijing 100034, China

关键词: Uniparental disomy;    Isodisomy 9;    Trisomy 9 mosaicism syndrome;    Quantitative fluorescent PCR;    Fluorescent in situ hybridization;    Karyotyping;    Prenatal diagnosis;    Noninvasive prenatal testing;   

Others  :  1221597
DOI  :  10.1186/s13039-015-0145-4

 received in 2015-03-24, accepted in 2015-04-25,  发布年份 2015

【 摘 要 】

Background

Non-invasive prenatal testing (NIPT) is currently used as a frontline screening test to identify fetuses with common aneuploidies. Occasionally, incidental NIPT results are conveyed to the clinician suggestive of fetuses with rare chromosome disease syndromes. We describe a child with trisomy 9 (T9) mosaicism where the prenatal history reported a positive NIPT result for T9 that was unconfirmed by conventional prenatal diagnosis.

Methods

NIPT was performed by low coverage whole genome plasma DNA sequencing. Karyotyping and fluorescent in situ hybridization (FISH) analysis with chromosome 9p-ter and 9q-ter probes was used to determine the somatic cell level of T9 mosaicism in the fetus and child. Quantitative fluorescent PCR (Q-PCR) of highly polymorphic short tandem repeat (STR) chromosome 9 markers was also performed to investigate the nature of the T9 mosaicism and the parental origin.

Results

A 22 month old girl presented with severe developmental delay, congenital cerebral dysplasia and congenital heart disease consistent with phenotypes associated with T9 mosaicism syndrome. Review of the prenatal testing history revealed a positive NIPT result for chromosome T9. However, follow up confirmatory karyotyping and FISH analysis of fetal cells returned a normal karyotype. Post-natal studies of somatic cell T9 mosaicism by FISH detected levels of approximately 20 % in blood and buccal cells. Q-PCR STR analysis of family DNA samples suggested that the T9 mosaicism originated by post-zygotic trisomic rescue of a paternal meiotic II chromosome 9 non-disjunction error resulting in the formation of two distinct somatic cell lines in the proband, one with paternal isodisomy 9 and one with T9.

Conclusion

This study shows that NIPT may also be a useful screening technology to increase prenatal detection rates of rare fetal chromosome disease syndromes.

【 授权许可】

   
2015 Ma et al.

【 图 表 】

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