To date, all of the chromosomal deletions that cause -thalassemia remove the structural genes and/or their regulatory element (HS –40). A unique deletion occurs in a single family that juxtaposes a region that normally lies approximately 18-kilobase downstream of the human cluster, next to a structurally normal -globin gene, and silences its expression. During development, the CpG island associated with the -globin promoter in the rearranged chromosome becomes densely methylated and insensitive to endonucleases, demonstrating that the normal chromatin structure around the -globin gene is perturbed by this mutation and that the gene is inactivated by a negative chromosomal position effect. These findings highlight the importance of the chromosomal environment in regulating globin gene expression.
Short stature and primary ovarian insufficiency possibly due to chromosomal position effect in a balanced X;1 translocation
