BACKGROUND: The clinical manifestations of trisomy 7 mosaicism are diverse and nonspecific, so prenatal diagnosis is very difficult.
METHODS: Two pregnant women with abnormal prenatal screening results were included. One was a 22-year-old woman (G1P0). At 31st week of gestation, ultrasound revealed that the posterior horn of the left lateral ventricle was 10 mm and the right renal pelvis had a separation of 7 mm. The other pregnant woman was 33 years old (G2P1L1A0), and her fetus was found to have a cardiac malformation at the 24th week of gestation. Copy number variation sequencing, whole-exome sequencing and karyotype analysis were carried out after amniocentesis, and both fetuses were diagnosed with trisomy 7 mosaicism. After parental counseling, one woman continued the pregnancy, and the other woman terminated the pregnancy.
CONCLUSIONS: In trisomy 7 mosaicism, the low proportion of trisomy does not lead to abortion, but can result in abnormal fetal development, which can be detected via ultrasound. Therefore, clinicians need to pay more attention to various aspects of fetal growth and development, combining with imaging, cellular, molecular genetics and other methods to perform comprehensive evaluations of fetuses to provide more reliable genetic counseling for pregnant women.

BACKGROUND: Quantitative fluorescent polymerase chain reaction (QF-PCR) is a rapid prenatal diagnostic method for abnormalities on chromosomes 21, 18, and 13 and sex chromosomal aneuploidy. However, the value of QF-PCR in diagnosing chromosomal structural abnormalities is limited. In this article, we report a confusing QF-PCR finding in a pregnant woman who underwent amniocentesis.
METHODS: The short tandem repeat marker AMXY (Xp22.2/Yp11.2) located on the sex chromosome exhibited a trisomic biallelic pattern, indicating that the karyotype of the fetus might be 47,XYY. Chromosome analysis performed on cultured amniocytes showed a normal male karyotype of the fetus. Copy number variation sequencing confirmed a 500 kb duplication at Yp11.2-Yp11.2 (chrY:6610001_ 7110000) and a 250 kb duplication at Yp11.2-Yp11.2 (chrY:7110001_7360000).
CONCLUSIONS: In conclusion, the comprehensive application of different methods could achieve a higher detection rate and accuracy for the prenatal diagnosis of chromosomal disorders through chromosomal testing.

Chromosomal mosaicism remains a perpetual diagnostic and clinical dilemma. In the present study, we detected two prenatal trisomy 9 mosaic syndrome cases by using multiple genetic testing methods. The non-invasive prenatal testing (NIPT) results suggested trisomy 9 in two fetuses. Karyotype analysis of amniocytes showed a high level (42%-50%) of mosaicism, and chromosomal microarray analysis (CMA) of uncultured amniocytes showed no copy number variation (CNV) except for large fragment loss of heterozygosity. Ultrasound findings were unmarkable except for small for gestational age. In Case 1, further umbilical blood puncture confirmed 22.4% and 34% trisomy 9 mosaicism by CMA and fluorescent in situ hybridization (FISH) respectively. After comprehensive consideration of the genetic and ultrasound results, the two gravidas decided to receive elective termination and molecular investigations of multiple tissue samples from the aborted fetus and the placenta. The results confirmed the presence of true fetoplacental mosaicism with levels of trisomy 9 mosaicism from 76% to normal in various tissues. These two cases highlight the necessity of genetic counseling for gravidas whose NIPT results highly suggest the risk of chromosome 9 to ascertain the occurrence of mosaicism. In addition, the comprehensive use of multiple genetic techniques and biological samples is recommended for prenatal diagnosis to avoid false-negative results. It should also be noted that ultrasound results of organs with true trisomy 9 mosaicism can be free of structural abnormalities during pregnancy.

Small supernumerary marker chromosomes (sSMCs) derived from the chromosome 6 short arm are rare and their clinical significance remains unknown. No case with sSMC(6) without centromeric DNA has been reported. Partial trisomy and tetrasomy of distal 6p is a rare but clinically distinct syndrome. We report on a de novo mosaic sSMC causing partial tetrasomy for 6p23-p25.3 in a male infant with symptoms of being small for gestational age, microcephaly, facial dysmorphism, congenital eye defects, and multi-system malformation. Conventional cytogenetic analysis revealed a karyotype of 47,XY,+mar [25]/46,XY [22]. Array comparative genomic hybridization (aCGH) revealed mosaic tetrasomy of distal 6p. This is the first case of mosaic tetrasomy 6p23-p25.3 caused by an inverted duplicated neocentric sSMC with characteristic features of trisomy distal 6p. Comparison of phenotypes in cases with trisomy and tetrasomy of 6p23-p25.3 could facilitate a genotype-phenotype correlation and identification of candidate genes contributing to their presentation. The presentation of anterior segment dysgenesis and anomaly of the renal system suggest triplosensitivity of the FOXC1 gene. In patients with microcephaly growth retardation, and malformation of the cardiac and renal systems, presentation of anterior segment dysgenesis might be indicative of chromosome 6p duplication, and aCGH evaluation should be performed for associated syndromic disease.

Background: Fetal congenital heart disease (CHD) is the most common congenital defect, with an incidence of 0.6-0.8%, accounting for 30-50% of infant congenital disease deaths. The pathogenesis of CHD is still unclear, so an active and effective prenatal diagnosis is very important for the prevention and control of CHD. Herein, a Chinese CHD patient with rare compound heterozygous mutations in the DNAH9 gene was reported, and the 3D structure and functional changes of DNAH9 protein were predicted. Case presentation: A 23-year-old pregnant woman came to our hospital for prenatal diagnosis at 27 weeks of gestation. Both she and her partner were unaffected. Fetal CHD was detected by ultrasound screening. Copy number variation sequencing (CNV-seq) revealed an 81 kb deletion at chr17p12 (11,486,795-11,568,385), including exons 1-15 of DNAH9 gene, which plays a key role in cardiac development. Then, whole exome sequencing (WES) was used and identified a nonsense mutation (c.10975C>T) in DNAH9, which resulted in the mutation of amino acid 3,659 from glutamine to termination. The 3D mutant protein structures were predicted using SWISS-MODEL and showed structural changes from functional β-sheet and α-helix to termination, respectively. Conclusion: We describe a case of fetal CHD caused by DNAH9 mutations and provide an effective diagnostic technique for identifying intragenic deletions. This diagnostic process can be implicated in prenatal diagnosis of CHD.