Isochromosomes

An isochromosome is a structural abnormality in which a chromosome has two identical arms, produced by misdivision of the centromere during cell division. As a result, the chromosome contains two copies of either the short arm (p) or the long arm (q) and lacks the other arm. Isochromosomes are typically denoted as i(chromosome) with the arm indicated in parentheses, for example i(12p) or i(18q).

Formation occurs when the centromere divides transversely instead of longitudinally, producing a chromosome that is duplicated in a mirror-image fashion. This can occur during meiosis or mitosis and may be detected in all or only some cells, leading to mosaicism in affected individuals.

Genetic consequences involve a dosage imbalance: there is duplication of genes on the arm that is duplicated and loss of genes on the missing arm. The phenotypic impact depends on the specific chromosome involved, the genes located on that arm, and whether the abnormal cell line is mosaic. In many cases, clinical features reflect dosage changes in crucial developmental genes and vary with tissue distribution.

Clinical relevance is notable in both congenital disorders and cancers. Pallister-Killian syndrome is associated with mosaic tetrasomy 12p due to an isochromosome 12p. Isochromosomes involving the q arm, such as i(18q) and i(7q), are observed in various hematologic malignancies and solid tumors. Detection relies on karyotyping, with additional confirmation by fluorescence in situ hybridization (FISH) or array-based analyses; mosaic forms may require sampling of affected tissues beyond peripheral blood.

See also: chromosomal aberration, mosaicism, trisomy, monosomy.