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

作者：Ma, Jingmei; Cram, David S.; Zhang, Jianguang; Shang, Ling; Yang, Huixia^*; Pan, Hong

来源：Molecular Cytogenetics, 2015, 8(1): 44.

DOI：10.1186/s13039-015-0145-4

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

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.

• 出版日期2015-6-26
• 单位北京大学