Detection of Isodisomy Utilizing SNP Microarray: Frequency, Ascertainment, and Implications

This study investigates the frequency, ascertainment, and clinical implications of whole chromosomal isodisomy using a database of over 415,000 chromosomal microarray (CMA) tests conducted since 2008 across prenatal, postnatal, and products of conception specimens. In this cohort, 0.04% of cases exhibited the rare chromosomal phenomenon of isodisomy. Analysis of these cases revealed distinct patterns in frequency, chromosome involvement, and parent of origin related to specimen type. Isodisomy 14 was most frequent in prenatal samples, while chromosomes 6, 7, and 15 were more common in postnatal cases. The involvement of imprinted and non-imprinted chromosomes was equivalent for prenatal cases, while imprinted chromosomes consisted of two-thirds of postnatal cases, with paternal uniparental isodisomy more prevalent than maternal across all specimen types. Several cases demonstrated unmasking of pathogenic variants in recessive genes, and findings support prior studies of associations between isodisomy 11 and prenatal or neonatal lethality. These results underscore the diagnostic value of CMA and contribute to an extended understanding of isodisomy's clinical relevance.