Microdeletion of 7p12.1p13, intellectual impairment, overgrowth and susceptibility to leukemia

Microdeletion of 7p12.1p13, including IKZF1 , causes intellectual impairment, overgrowth, and susceptibility to leukemia.

Mutations within the IKZF1 gene cause a number of severe symptoms, including hypogammaglobulinemia, B cell deficiency (a lack of B cells, which negatively affects the immune system), and a predisposition to childhood leukemia, including B cell precursor acute lymphoblastic leukemia (BCP-ALL). This article describes a family with an inherited 6.7 Mb deletion in 7p12.1p13 – or, a deletion within the p12.1 and p13 regions of the short arm of chromosome 7 – that includes loss of the IKZF1 gene. Mother and her two children revealed intellectual disability, facial dysmorphism and overgrowth (higher BMI and head circumference). Dysmorphic features included flared eyebrows, a thin upper lip, hypertelorism (abnormally wide-set eyes), a broad forehead, and a wide nasal bridge. Both children developed BCP-ALL.

The deletion in this family encompasses 31 genes, including IKZF1, which is most likely responsible for the predisposition to BCP-ALL. However, the additional symptoms shared by this family – overgrowth and intellectual disability – may be caused by the other 30 genes within this deletion. For example, GRB10 is another gene found within this region. GRB10 is a growth receptor binding protein, and loss of this gene may result in abnormal growth. Therefore, loss of the GRB10 gene is a likely cause for the overgrowth symptom, but more research needs to be done to confirm this assumption.

This study gives further evidence to the hypothesis that IKZF1 loss is a major contributor to ALL susceptibility in the 7p12.1p13 deletion carriers. This evidence in the role of IKZF1 in leukemia development can eventually help in producing better preventative screens and treatment options for these cases.

Järviaho, et al. “Microdeletion of 7p12.1p13, including IKZF1 , causes intellectual impairment, overgrowth, and susceptibility to leukaemia”. British Journal of Haematology 2018, in press.

Newly published research articles are selected and reviewed monthly by Dr. Iosif Lurie, M.D, PhD