Cytogenetic and molecular genetic analysis of small supernumerary marker chromosomes in fetal amniotic fluid

Abstract

To explore the origin and mechanism of small supernumerary marker chromosomes (sSMC) in order to facilitate genetic counseling. Chromosome karyotypes of two fetuses and their immediate family members were analyzed by conventional G banding. High-throughput whole genome sequencing was used to determine the origin of sSMCs. Fetus 1 was shown to have a karyotype of 47,XY,+mar but with normal FISH and B ultrasound findings. Its father also had a 47,XY,+mar karyotype with normal FISH results and clinical phenotype. High-throughput genome sequencing revealed that fetus 1 and its father were both 46,XY,dup(21)(q11.2;q21.1) with a 6.2 Mb duplication of the long arm of chromosome 21. The fetus was born with normal phenotype and developed well. Its grandmother also had a karyotype of 46,XX,t(15;21)(q13;p13) with normal FISH result and clinical phenotype. The karyotypes of its mother and grandfather were both normal. Analysis of fetus 2 showed a 47,XY,+mar karyotype with normal FISH results. High-throughput genome sequencing suggested a molecular karyotype of 46,XX. The fetus was born with normal phenotype and developed well. The karyotypes of its parents were both normal. Considering their variable origins, identification of sSMC should combine conventional G banding analyses with high-throughput whole genome sequencing for precise delineation of the chromosomes.