Identification of an individual with a SYGNAP1 pathogenic mutation in India

Exome sequencing is a prominent tool to identify novel and deleterious mutations which could be non-sense, frameshift, and canonical splice-site mutations in a specific gene. De novo mutations in SYNGAP1, which codes for synaptic RAS-GTPase activating the protein, causes Intellectual disability (ID) and Autism Spectrum Disorder (ASD). SYNGAP1 related ASD/ID is one of the rare diseases that are detrimental to the healthy neuronal developmental and disrupts the global development of a child. We report the first SYNGAP1 heterozygous patient from Indian cohort. We report a case of a child of 2-year old with global developmental delay, microcephaly subtle dysmorphism, absence seizures, disrupted sleep, delay in learning a language, and eating problems. Upon further validation, the child has a few traits of ASD. Here, based on focused exome sequencing, we report a de novo heterozygous mutation in SYNGAP1 exon 11 with c. 1861 C > T (p.arg621ter). Currently, the child is on Atorvastatin, a RAS inhibitor, already available in the market for the treatment of hypercholesterolemia and has shown considerable improvement in global behaviour and cognitive development. The long-term follow up of the child's development would contribute to the already existing knowledge of the developmental trajectory in individuals with SYNGAP1 heterozygous mutation. In this report, we discuss the finding of a novel mutation in one of the genes, SYNGAP1, implicated in ASD/ID. Besides, we discuss the current treatment prescribed to the patient and the progress of global developmental of the child.