Chromosome 7p22 deletion and associated symptoms directly caused by the loss of gene ACTB.
7p22 deletion – a deletion within the short arm of chromosome 7 – causes a number of symptoms, including developmental delay, intellectual disability, internal organ malformations (primarily within the heart and kidneys), and facial abnormalities. These facial abnormalities include dense eyelashes, wide nose, wide mouth, and a prominent chin. Within the 7p22 region is ACTB , a gene which encodes the protein β-actin. The article hypothesizes that loss of ACTB causes the symptoms of the 7p22 deletion.
To test this idea, the study surveyed 33 individuals with loss of the ACTB gene (either from a 7p22 deletion, or from a mutation within the gene itself) and analyzed their clinical symptoms. As predicted, the individuals with the loss of ACTB were described as having basically the same symptoms mentioned above. In several individuals, speech was greatly affected. Some were also reported to exhibit autism spectrum disorder and attention-deficit hyperactivity disorder. Congenital heart defects were found in about half of patients.
The ACTB gene encodes for a protein called β-actin, which is expressed throughout the body and is involved with a number of processes. β-actin is particularly important during development, as it regulates cell shape and migration. Actin is also a major structural component of synapses, a feature of nerve cells in the brain. Synapses directly affect neurodevelopment, cognitive performance, and social behavior, which could explain why lack of proper formation can result in the neurological symptoms mentioned above.
Although 7p22 deletions have been described previously, ACTB loss has not be proven to be the root of the symptoms. The article concludes by stating that a loss of ACTB directly causes of the symptoms of the 7p22 deletion. The reason being that loss of β-actin alters cell shape, growth, and migration, which greatly inhibits proper development.
Cuvertino et al. “ ACTB Loss-of-Function Mutations Result in a Pleiotropic Developmental Disorder”. The American Journal of Human Genetics 2017, v. 101, 1021-1033.