A RARE CAUSE OF AUTISM AND EPILEPSY COMBINATION: GRM7 GENE MUTATION

İntroduction GRM7 gene mutation is a rare autosomal recessive mutation and causes defects in metabotropic glutamate receptors. GRM7 gene mutations may cause developmental delay, microcephaly, epilepsy, hypotonia, hyperreflexia, nutritional disorders, autism, attention deficit and hyperactivity disorders. We described two siblings with autism, mental retardation, epilepsy and GRM7 gene mutation. Methods Two brothers (13-yeras old,17 years old) borned to nonconsangious family, admitted to our hospital with autism and epilepsy. Their sizures were strarted in the two years of life. Microcephaly, tetraparesis and mental retardation was revelaed in neurologic examinations of patients. Metabolic screening tests were normal. Cranial magnetic resonance imaging (MR) was normal in the former and revealed hyperintensity in the periventricular area in diffuse T2-Flair examination in the latter patient. Frequent generalized discharges on the basis of diffuse disorganization revealed in electroencehalography ( EEG) examination. In next generation sequencing genetic tests GRM7 c.2671G>A p.Glu891Lys missense mutation was revealed in both patients. Results Glutamate is an excitatory neurotransmitter that acts through two main receptor groups: ionotropic glutamate receptors (iGluRs) and metabotropic glutamate receptors (mGluRs). Glutamate receptor 7 (mGluR7), encoded by GRM7, is a presynaptic G protein downregulates calcium-dependent glutamate release and thus prevent the neurotoxic effect of extracellular glutamate accumulation. mGluR7 is widely distributed in the the hippocampus, hypothalamus, and thalamo-cortical circuitry synapses. GRM7 gene mutations can cause epilepsy, auıtism, mental retardation and pyramidal symptoms. CONCLUSION Next generation genetic tests should be considered in patiens with epilepsy, auıtism, mental retardation and in whom cranial MRI is normal.
Keywords: GRM7 gene, autism, epilepsy