Autism, Still A Medical Mystery?
Running Title: Autism Spectrum Disorder (ASD) and Genetic Features: Importance in Clinical Medicine!
1Department of Stem Cells, Oncology and Nanomedicine
In 1943, the well-known child psychiatrist, Leo Kanner, announced his discovery of eleven cases of a new mental disorder . He noted that «the condition differs markedly and uniquely from anything reported so far...»This condition soon became known as autism.
Indeed, recent studies implicate chromatin modifiers in ASD through the identification of recurrent de novo loss of function mutations in affected individuals. ASD risk genes [(i.e. CHD8 (chromodomain helicase DNA binding protein 8, 14q11.2) binding genes such as GRIN2B (glutamate receptor, ionotropic, N-methyl D-aspartate 2B, 12p12) ] are co-expressed in human mid-fetal cortex, suggesting that ASD risk genes converge in specific regulatory networks during neurodevelopment . Interestingly, one of the more frequent genetic anomalies is found on chromosome 15 (i.e. duplicated or triplicated region 15q11-q13 where several genes such as maternally expressed UBE3A (Ubiquitin-protein ligase E3A) linked to Angelman syndrome, MECP2 (methyl CpG binding protein 2) linked to Rett syndrome, and the non-imprinted GABRB3, a gamma-aminobutyric acid (GABA(A)) receptor subunit associated with synaptic plasticity) are thought to be involved in autism [9,10]. Recent studies showed that many genes associated with language abnormalities in autism are also found in schizophrenia. Thereby, many functional genes, for example, FOXP2 (forkhead box protein P2; 7q31), a transcription factor involved in the development of several tissues, including the brain. COMT (Catechol-O-methyltransferase, 22q11), GABRB3, and DISC1 (Disrupted in schizophrenia 1, 1q42.1) are actually implicated in both of them . Also, an emerging phenotype of autism patients with protein-disrupting FOXP1 (3p14.1) variants includes global developmental delay, intellectual disability and mild to severe speech/language deficits . Interestingly, some genomic sequences are associated with severe autism. These include the adhesive junction-associated δ-catenin protein CTNND2, which plays a critical role in neuronal development, has an intimate connection to chromatin biology, and for which the loss of function have been noticed in female-enriched multiplex families ; Sequences encoding DUF1220 protein domains (i.e. DUF1220 subtype CON1) exhibit an exceptional human-specific increase in copy number and have been associated with several phenotypes related to brain size, particularly in children .
Cite this article: Farid Menaa. Autism, Still A Medical Mystery? J J Gene. 2015, 1(1): 001.