Vertical inheritance and unique differential phenotypes of reciprocal recombinant chromosome 18 within a multi-generation family
Recommended Citation
Wen T, Akay G, Palumbos J, Ostrander B, Quigley DI, Lamb AN, Andersen EF, Hong B, and Viskochil D. Vertical inheritance and unique differential phenotypes of reciprocal recombinant chromosome 18 within a multi-generation family. Eur J Hum Genet 2025.
Document Type
Article
Publication Date
7-8-2025
Publication Title
European journal of human genetics : EJHG
Abstract
Carriers of balanced pericentric inversions are at risk for producing unbalanced gametes because of meiotic recombination resulting in de novo deletion and duplication of distal chromosome ends. Recombinant chromosomes generally lead to significant imbalances resulting in anomalous clinical phenotypes in offspring, hence they are typically not inherited. Therefore, the vertical transmission of recombinant chromosomes is a clinically rare event. Using genomic microarray and karyotyping, we describe inheritance of recombinant chromosomes in a three-generation family with the grandmother carrying a mosaic pericentric inversion of chromosome 18. Three children inherited the balanced inversion and one child with a mild phenotype inherited a de novo recombinant chromosome 18. In the third generation, a newborn with a variant of holoprosencephaly inherited an unmodified recombinant chromosome from her mother. Despite having the same karyotype predicting loss of the TGIF1 gene from the 18p terminus, the mother exhibits a relatively unaffected phenotype. The cousin of the child with holoprosencephaly carries the reciprocal recombinant chromosome 18 with a much milder phenotype. We verified the cytogenetic mechanism and corresponding clinical phenotypes in affected individuals and illustrated possible recombinant chromosome consequences of the inversion of chromosome 18 in this three-generation family.
PubMed ID
40628998
ePublication
ePub ahead of print
