Mutation in the DEAF1 gene is also linked to basal ganglia dysfunction and epilepsy, beside autism and intellectual disability. This finding was published in a 2015 issue of Journal of Medical Genetics.
There are several genetic defects that can cause autism-related intellectual disability and epilepsy. The published article describes a defect in the DEAF1 gene in three children from an Omani family in whom mutations in known candidate genes were not present. Severe epilepsy was observed in two of three children, apart from intellectual disability and autism. Movement disorder affecting the limbs was present in all three siblings. This occurred due to changes in a part of the nervous system called the basal ganglia; the changes were demonstrated on MRI.
AdvertisementBased on genetic studies, the researchers found that all affected individuals showed a mutation in the DEAF1 gene (c.997+4A>C, p.G292Pfs*). The researchers also stated that DEAF-1 linked disorder can be hereditary and inherited as an autosomal recessive trait. A condition is said to be inherited in a recessive manner if it manifests clinically only when the defect is present on both the pair of chromosomes. The researchers also indicated that DEAF1 mutations can result in epilepsy and extrapyramidal symptoms like abnormal movements, as shown in these patients.
The DEAF 1 gene is officially named as 'DEAF1 transcription factor'. It encodes a protein which is necessary for embryonic development. The gene is located on the short arm of chromosome 11. Mutations in the gene have been associated with mental retardation. A study had previously demonstrated that de novo mutations in the SAND domain of DEAF1 can cause intellectual disability with severe speech impairment and behavioral problems. Patients with DEAF1 mutations can be managed by treating clinical manifestations of the genetic defect.
References:1. Rajab A. et.al. Recessive DEAF1 mutation associates with autism, intellectual disability, basal ganglia dysfunction and epilepsy. J Med Genet. 2015 Sep; 52(9):607-11.
2. Vulto-van Silfhout AT, et.al. Mutations Affecting the SAND Domain of DEAF1 Cause Intellectual Disability with Severe Speech Impairment and Behavioral Problems. Am J Hum Genet. 2014; 94(5): 649-661.
3. DEAF1. Genetics Home Reference. Available from http://ghr.nlm.nih.gov/gene/DEAF1