Biallelic variants in SLC38A3 encoding a glutamine transporter cause epileptic encephalopathy

The solute carrier (SLC) superfamily encompasses >400 transmembrane transporters involved in the exchange of amino acids, nutrients, ions, metals, neurotransmitters and metabolites across biological membranes. SLCs are highly expressed in the mammalian brain; defects in nearly 100 unique SLC-encoding genes (OMIM: https://www.omim.org) are associated with rare Mendelian disorders including developmental and epileptic encephalopathy (DEE) and severe neurodevelopmental disorders (NDDs). Exome sequencing and family-based rare variant analyses on a cohort with NDD identified two siblings with DEE and a shared deleterious homozygous splicing variant in SLC38A3. The gene encodes SNAT3, a sodium-coupled neutral amino acid transporter and a principal transporter of the amino acids asparagine, histidine, and glutamine, the latter being the precursor for the neurotransmitters GABA and glutamate. Additional subjects with a similar DEE phenotype and biallelic predicted-damaging SLC38A3 variants were ascertained through GeneMatcher and collaborations with research and clinical molecular diagnostic laboratories. Untargeted metabolomic analysis was performed to identify novel metabolic biomarkers. Ten individuals from seven unrelated families from six different countries with deleterious biallelic variants in SLC38A3 were identified. Global developmental delay, intellectual disability, hypotonia, and absent speech were common features while microcephaly, epilepsy, and visual impairment were present in the majority. Epilepsy was drug-resistant in half. Metabolomic analysis revealed perturbations of glutamate, histidine, and nitrogen metabolism in plasma, urine, and cerebrospinal fluid of selected subjects, potentially representing biomarkers of disease. Our data support the contention that SLC38A3 is a novel disease gene for DEE and illuminate the likely pathophysiology of the disease as perturbations in glutamine homeostasis

Suitability of the predatory mites Iphiseiodes zuluagai and Euseius concordis in controlling Polyphagotarsonemus latus and Tetranychus bastosi on Jatropha curcas plants in Brazil

One of the most promising plant species for biofuel production in Brazil is the physic nut Jatropha curcas. Major phytosanitary problems include the attack of two pest mite species, the broad mite Polyphagotarsonemus latus and the spider mite Tetranychus bastosi. Owing to pesticide-related problems, there is an increasing demand for sustainable environmental-friendly control methods such as biological control. In this study we evaluated the suitability of the predatory mite species Iphiseiodes zuluagai and Euseius concordis in controlling P. latus and T. bastosi on J. curcas. The number of T. bastosi killed by I. zuluagai was lower than the number of P. latus consumed.Euseius concordis preyed upon both T. bastosi and P. latus but the number of prey killed was always lower in comparison with I. zuluagai. However, P. latus and T. bastosi are suitable for the development of I. zuluagai and E. concordis as oviposition of both predators did not differ in relation to prey species. The preference of I. zuluagai for leaves of plants infested by either P. latus or T. bastosi, combined with the higher values for predation obtained by this predatory mite when fed on P. latus, compared to those values obtained by E. concordis, suggests that I. zuluagai can be more efficient than E. concordis in reducing populations of P. latus and T. bastosi under field conditions. Furthermore, we report here on the first record of predatory mites associated with P. latus and T. bastosi on native J. curcas plants in Brazil. In conclusion, we emphasize the crucial importance of predatory mites as agents of natural biological control of mite pests on J. curcas in small farms