Background: Karyotyping is the gold standard cytogenetic method for detection of ring chromosomes. In this study we report the molecular characterization of a novel ring 6 (r6) chromosome in a six-year-old girl with severe mental retardation, congenital heart disease and craniofacial abnormalities.
Methods: Cytogenetic analysis was performed by conventional karyotyping. Molecular genetic analyses were performed using high-resolution chromosome microarray analysis (CMA) and next generation sequencing (NGS). OMIM, UCSC and PubMed were used as reference databases to determine potential genotype to phenotype associations.
Results: Peripheral blood and skin fibroblast karyotyping revealed the presence of a dominant cell line, 46,XX,(r6)(p25.3;q27) and a minor cell line 45,XX,-6. Molecular karyotyping using NGS identified 6p25.3 and 6q27 subtelomeric deletions of 1.78 Mb and a 0.56 Mb, respectively. Based on the known genes located within the r6 deletion interval 6q25.3-pter, genotype to phenotype association studies found compelling evidence to suggest that hemizygous expression of disease genes FOXC1, FOXF2, IRF4 and GMDS was the main underlying cause of the patient's phenotype. We further speculate that the severity of the patient's symptoms may have been exacerbated by low-level instability of the r6 chromosome.
Conclusion: This is the first report of a novel r6 chromosome characterized at the molecular level using NGS.
Keywords: Chromosome microarray analysis; Copy number variation; Karyotyping; Next generation sequencing; Ring chromosome.