Identification of an individual with a SYGNAP1 pathogenic mutation in India
- PDF / 1,853,022 Bytes
- 10 Pages / 595.276 x 790.866 pts Page_size
- 40 Downloads / 170 Views
SHORT COMMUNICATION
Identification of an individual with a SYGNAP1 pathogenic mutation in India Vijaya Verma1 · Amit Mandora2 · Abhijeet Botre3 · James P. Clement1 Received: 2 April 2020 / Accepted: 10 October 2020 © Springer Nature B.V. 2020
Abstract 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. Keywords SYNGAP1 · Autism spectrum disorder · Intellectual disability · Epilepsy · Neurodevelopmental disorder · Case report
Introduction ID and ASD are common debilitating neurodevelopmental disorders defined by the presence of significant limitations in cognitive and emotional behaviours, and global delay in development associated with epilepsy [1–4]. Heterozygous mutations in SYNGAP1 causing ID and ASD was first reported in 2009 [1]. Since then, many exome sequencings studies have identified novel mutations in SYNGAP1 [3, 5, 6]. Most affected individuals have de novo mutations with
* James P. Clement [email protected] 1
Neuroscience Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore 560064, India
2
SYNGAP1 Research Foundation, Pune, India
3
Paediatric Neurology and Epilepsy, KEM Hospital, Pune, India
truncating mutations, but missense mutations, chromosomal aberrations and microdeletions in SYNGAP1 are reported [7–10]. SYNGAP1-related ASD/ID is recently categorised as rare-diseases. SYNGAP1 on chromosome 6p21.32 (OMIM 603,384) encodes a synaptic RAS-GTPase activating protein expressed mainly in the excitatory neurons [11, 12]. SYNGAP1 is a vital regulator of
Data Loading...
