A familial chromosomal complex rearrangement confirms RUNX1T1 as a causative gene for intellectual disability and suggests that 1p22.1p21.3 duplication is likely benign

摘要

Complex chromosomal rearrangements are constitutive structural aberrations involving three or more breaks. They can be balanced or unbalanced and result in different outcomes, depending on deletion/duplication of genomic material, gene disruption, or position effects. We report on a patient presenting with severe anemia, splenomegaly, mild intellectual disability and facial dysmorphisms harboring a 4.3?Mb duplication at 1p22.1p21.3 and a 2.1?Mb deletion at 8q21.3q22.1, involving RUNX1T1 gene. The healthy brother presented the same duplication of chromosome 1p as at 1p22.1p21.3. The rearrangement found both these siblings resulted from malsegregation in the proband and recombination in her healthy brother of a balanced paternal complex chromosomal rearrangement. These results confirm RUNX1T1 as a causative gene for intellectual disability and suggest the 1p22.1p21.3 duplication is likely benign.