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Autism spectrum disorder (ASD) is a neurological condition that directly affects brain functions and can culminate in delayed intellectual development, problems in verbal communication, difficulties in social interaction, and stereotyped behaviors. Its etiology reveals a genetic basis that can be strongly influenced by socio-environmental factors. Ion channels controlled by ligand voltage-activated calcium, sodium, and potassium channels may play important roles in modulating sensory and cognitive responses, and their dysfunctions may be closely associated with neurodevelopmental disorders such as ASD. This is due to ionic flow, which is of paramount importance to maintaining physiological conditions in the central nervous system and triggers action potentials, gene expression, and cell signaling. However, since ASD is a multifactorial disease, treatment is directed only to secondary symptoms. Therefore, this research aims to gather evidence concerning the principal pathophysiological mechanisms involving ion channels in order to recognize their importance as therapeutic targets for the treatment of central and secondary ASD symptoms.

Background and aims GPIHBP1 is an accessory protein of lipoprotein lipase (LPL) essential for its functioning. Mutations in the GPIHBP1 gene cause a deficit in the action of LPL, leading to severe hypertriglyceridemia and increased risk for acute pancreatitis. Methods We describe twelve patients (nine women) with a novel homozygous mutation in intron 2 of the GPIHBP1 gene. Results All patients were from the Northeastern region of Brazil and presented the same homozygous variant located in a highly conserved 3′ splicing acceptor site of the GPIHBP1 gene. This new variant was named c.182-1G > T, according to HGVS recommendations. We verified this new GPIHBP1 variant's effect by using the Human Splicing Finder (HSF) tool. This mutation changes the GPIHBP1 pre-mRNA processing and possibly causes the skipping of the exon 3 of the GPIHBP1 gene, affecting almost 50% of the cysteine-rich Lys6 GPIHBP1 domain. Patients presented with severe hypertriglyceridemia (2351 mg/dl [885–20600]) and low HDL (18 mg/dl [5–41). Four patients (33%) had a previous history of acute pancreatitis. Conclusions We describe a novel GPIHBP1 pathogenic intronic mutation of patients from the Northeast region of Brazil, suggesting the occurrence of a founder effect.