Background: Defining the phenotype-genotype correlation of small supernumerary marker chromosomes (sSMCs) remains a challenge in prenatal diagnosis. We karyotyped 20,481 amniotic fluid samples from pregnant women and explored the molecular characteristics of sSMCs using a single nucleotide polymorphism (SNP) array. Results: Out of the 20,481 samples, 15 abnormal karyotypes with sSMC were detected (frequency: 0.073%) and the chromosomal origin was successfully identified by SNP array in 14 of them. The origin of sSMCs were mainly acrocentric-derived chromosomes and the Y chromosome. Two cases of sSMC combined with uniparental disomy (UPD) were detected, UPD(1) and UPD(22). More than half of the cases of sSMC involved mosaicism (8/15) and pathogenicity (9/15) in prenatal diagnosis. A higher prevalence of mosaicism for non-acrocentric chromosomes than acrocentric chromosomes was also revealed. One sSMC derived from chromosome 3 with a neocentromere revealed a 24.99-Mb pathogenic gain of the 3q26.31q29 region on the SNP array, which presented as an abnormal ultrasound indicating nasal bone hypoplasia. Conclusion: The clinical phenotypes of sSMCs are variable and so further genetic testing and parental karyotype analysis are needed to confirm the characteristics of sSMCs. The SNP array used here allows a detailed characterisation of the sSMC and establishes a stronger genotype-phenotype correlation, thus allowing detailed genetic counselling for prenatal diagnosis.
Background The phenotypes of uniparental disomy (UPD) are variable, which may either have no clinical impact, lead to clinical signs and symptoms. Molecular analysis is essential for making a correct diagnosis. This study involved a retrospective analysis of 4512 prenatal diagnosis samples and explored the molecular characteristics and prenatal phenotypes of UPD using a single nucleotide polymorphism (SNP) array. Results Out of the 4512 samples, a total of seven cases of UPD were detected with an overall frequency of 0.16%. Among the seven cases of UPD, two cases are associated with chromosomal aberrations (2/7), four cases (4/7) had abnormal ultrasonographic findings. One case presented with iso-UPD (14), and two case presented with mixed hetero/iso-UPD (15), which were confirmed by Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) as maternal UPD (15) associated with Prader-Willi syndrome (PWS). Four cases had iso-UPD for chromosome 1, 3, 14, and 16, respectively; this is consistent with the monosomy rescue mechanism. Another three cases presented with mixed hetero/isodisomy were consistent with a trisomy rescue mechanism. Conclusion The prenatal phenotypes of UPD are variable and molecular analysis is essential for making a correct diagnosis and genetic counselling of UPD. The SNP array is a useful genetic test in prenatal diagnosis cases with UPD.
Background With the application of chromosome microarray, next-generation sequencing and other highly sensitive genetic techniques in disease diagnosis, the detection of mosaicism has become increasingly prevalent. This study involved a retrospective analysis of SNP array testing on 4512 prenatal diagnosis samples, wherein the characterization of mosaicism was explored and insights were gained into the underlying mechanisms thereof. Results Using SNP array, a total of 44 cases of mosaicism were identified among 4512 prenatal diagnostic cases; resulting in a detection rate of approximately 1.0%. The prevalence of mosaicism was 4.1% for chorionic villus sample, 0.4% for amniotic fluid, and 1.3% for umbilical cord blood. Of these cases, 29 were mosaic aneuploidy and 15 were mosaic segmental duplication/deletion. Three cases of mosaic trisomy 16 and three cases of mosaic trisomy 22 were diagnosed in the CVS samples, while four cases of mosaic trisomy 21 were detected in amniotic fluid and umbilical cord blood samples. The distribution pattern of mosaicism suggested trisomy rescue as the underlying mechanism. Structurally rearranged chromosomes were observed, including three cases with supernumerary marker chromosomes, three cases with dicentric chromosomes, and one case with a ring chromosome. All mosaic segmental duplication/deletion cases were the result of mitotic non-disjunction, with the exception of one case involving mosaic11q segmental duplication. Conclusion Improved utilization of SNP arrays enables the characterization of mosaicism and facilitates the estimation of disease mechanisms and recurrence.
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