[Genetic analysis of two fetuses with supernumerary small marker chromosomes derived from complex chromosomal...

To report on two fetuses with supernumerary small marker chromosomes (sSMC) derived from complex rearrangements and explore their genotype-phenotype correlation.

Two pregnant women who presented at the Prenatal Diagnosis Center of Taizhou Hospital of Zhejiang Province for a high risk signaled by noninvasive prenatal testing (NIPT) were selected as study subjects. Amniotic fluid and peripheral blood samples were collected and subjected to chromosomal karyotyping analysis and copy number variation sequencing (CNV-seq). Databases were searched for similar cases reported in the literature, and the correlation between genotype and phenotype was analyzed. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: K20250822).

The karyotype of fetus 1 was identified as 47,XY,+der(22)t(11;22)(q23.3;q11.2)dmat. CNV-seq analysis revealed an 18.1 Mb duplication in the 11q23.3q25 region and a 4.26 Mb duplication in the 22q11.1q11.21 region. The fetus was diagnosed with Emanuel syndrome, and the der(22) has originated from a balanced translocation t(11;22)(q23;q11.2) carried by the mother. The karyotype of fetus 2 was determined as 47,XY,+mar mat, and CNV-seq indicated a 13.06 Mb duplication in the 18p11.32p11.21 region. The fetus' partial 18p trisomy was inherited from its phenotypically normal mother.

NIPT has value in screening for fetuses with sSMCs. Chromosomal karyotyping combined with CNV-Seq can elucidate the size and genetic content of the sSMCs, thereby facilitating prenatal diagnosis and genetic counseling. Prenatal findings for fetuses with Emanuel syndrome primarily include posterior cranial fossa abnormalities, ventricular enlargement, cardiac developmental anomalies, and increased nuchal translucency. Trisomy 18p caused by sSMC is associated with mild malformations.