Marker chromosomes in 15 individuals: cytogenetic delineation and molecular findings from SNP array analysis in a subset of cases

Abstract

Abstract Objective Marker chromosomes (MCs) are structurally abnormal chromosomes that can be detected by standard cytogenetic banding techniques but their precise structure and origin cannot be fully determined by these methods alone. These abnormal chromosomes can be present as supernumerary chromosomes in an otherwise normal karyotype or replace a normal chromosome in a structurally abnormal karyotype. MCs can originate from any of the 24 chromosomes, which makes genotype-phenotype correlation a challenge in clinical diagnosis and genetic counseling for MCs carriers. In this study, we combined cytogenetic and molecular diagnostic techniques to determine the origin of MCs. By correlating the associated genomic variations with clinical phenotypes, we aimed to provide preliminary evidence-based medical guidance for individuals carrying MCs. Methods We retrospectively reviewed 15 cases of marker chromosomes (MCs) identified by conventional cytogenetic testing among 9,733 individuals at our center. A subset of these cases was further analyzed by single nucleotide polymorphism (SNP) array to determine the precise origin, size, and genomic content of the MCs. Results In this cohort, 15 carriers of marker chromosomes (MCs) were identified, including 13 with mosaic and 2 with non-mosaic karyotypes. Seven of these patients underwent molecular analysis. Of these, SNP array revealed that five carried MCs derived from the X/Y chromosomes. In one case, a duplicated fragment at 11p11.12q12.2 was identified, whereas in another, no copy number variations (CNVs) were detected by SNP array. The clinical phenotypes of the eight postnatal MC carriers were diverse, ranging from asymptomatic to severe growth and developmental delay. Observed manifestations included short stature, primary amenorrhea, and infertility. Conclusion Marker chromosomes (MCs) exhibit substantial genetic and clinical heterogeneity. The combined use of karyotyping and SNP array analysis effectively determined their chromosomal origin and facilitated the assessment of their pathogenic potential. Clinical outcomes were found to be strongly associated with the structure, chromosomal origin, and mosaic ratio of the MCs. This integrated diagnostic approach enables more accurate genotype-phenotype correlation and facilitates informed genetic counseling for affected individuals.