Molecular delineation of small supernumerary marker chromosomes using a single nucleotide polymorphism array

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.