Exome sequencing shed light on new disease causing genes; GAD2 as possible novel candidate for cerebellar palsy

Next-generation sequencing provides great accessibility and feasibility to finding known and unknown disease-causing genes in patients suffering genetic diseases. The comprehensive view and highly accurate data provision, and affordable availability cause rapidly growing implementation of this technology in clinical and research laboratories. Here we applied exome sequencing to a patient with neurodevelopmental disease suspected to have cerebral palsy (CP). Followed exome data analysis we found a homozygous missense variation (g.64773A> G) in GAD2 gene. Sanger sequencing approved that patient is homozygous and her healthy parents are heterozygous for this variation. On the other hand, these variant has not been found in our homemade database (800 WES). In-silico analysis showed this variant is pathogenic and potentially is disease causing. This gene encodes one of several forms of glutamic acid decarboxylase.GAD2 highly specially expressed in brain cells. Notably Gad2 knockout mice showed sensitized pain behavior, impaired GABA synaptic function in their brainstem neurons and increase in susceptibility to seizures. The enzyme coded from GAD2 has also been implicated as an autoantigen in the autoimmune disease stiff person syndrome (SPS; 184850). In conclusion it seems that GAD2 gene could be a new candidate to causes inherited neurodevelopmental diseases; CP. New generation of sequencing has opened a new way to profiling molecular statue of complicated diseases. Particularly in this new filed, whole exome sequencing shed light on many unresolved diagnosis and characterization of genetic diseases.