BCL11A deletions result in fetal hemoglobin persistence and neurodevelopmental alterations

Original research article by A. Basak et al. (2015).

Read the article here.

Fetal hemoglobin (HbF) is a protein that carries oxygen from a mother to her unborn baby. The BCL11A gene is responsible for limiting the amount of HbF produced after birth and for transitioning blood cells to produce adult hemoglobin while the fetus is developing. Disruptions in the function of BCL11A may increase HbF levels, and so thus disrupting its function shows promise as therapy for people with disorders affecting oxygen transport in the blood (such as sickle cell disease or beta-thalassemia. However, recent studies have also shown that changes in this gene may also be associated with autism spectrum disorder and developmental delay.

To better understand the impact of genetic changes involving BCL11A, the authors identified three people who have deletions in the BCL11A gene, not inherited from either parent. All three people have autism, moderate to severe developmental delay, low muscle tone, and differences in their facial features. Two of the people have small head size, and two of them, as they got older, developed problems with coordination, fine motor skills, hyperactivity, and aggression. All three were found to have significantly increased levels of HbF as well.

Since autism and developmental delay can be associated with increased risks for other neurodevelopmental disorders, the study team also looked at genetic data from a recent study of schizophrenia. They found a relatively high number of cases with genetic changes in the region of the BCL11A gene. While disrupting the BCL11A gene may be useful in increasing the levels of HbF, this study provides evidence that changes to this gene also contribute to neurodevelopmental disorders such as autism, developmental delay, attention deficit hyperactivity disorder, and schizophrenia. Caution must be taken when targeting this gene as a potential therapy for people with hemoglobin disorders.