PLXNA2 and LRRC40 as candidate genes in autism spectrum disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disability with high heritability yet the genetic etiology remains elusive. Therefore, it is necessary to elucidate new genotype-phenotype relationships for ASD to improve both the etiological knowledge and diagnosis. In this work, a copy-number variant and whole-exome sequencing analysis were performed in an ASD patient with a complex neurobehavioral phenotype with epilepsy and attention deficit hyperactivity disorder. We identified rare recessive single nucleotide variants in the two genes, PLXNA2 encoding Plexin A2 that participates in neurodevelopment, and LRRC40, which encodes Leucine-rich repeat containing protein 40, a protein of unknown function. PLXNA2 showed the heterozygous missense variants c.614G>A (p.Arg205Gln) and c.4904G>A (p.Arg1635Gln) while LRRC40 presented the homozygous missense variant c.1461G>T (p.Leu487Phe). In silico analysis predicted that these variants could be pathogenic. We studied PLXNA2 and LRRC40 mRNA and proteins in fibroblasts from the patient and controls. We observed a significant PlxnA2 subcellular delocalization and very low levels of LRRC40 in the patient. Moreover, we found a novel interaction between PlxnA2 and LRRC40 suggesting that participate in a common neural pathway. This interaction was significant decreased in the patient's fibroblasts. In conclusion, our results identified PLXNA2 and LRRC40 genes as candidates in ASD providing novel clues for the pathogenesis. Further attention to these genes is warranted in genetic studies of patients with neurodevelopmental disorders, particularly ASD. LAY SUMMARY: Genomics is improving the knowledge and diagnosis of patients with autism spectrum disorder (ASD) yet the genetic etiology remains elusive. Here, using genomic analysis together with experimental functional studies, we identified in an ASD complex patient the PLXNA2 and LRRC40 recessive genes as ASD candidates. Furthermore, we found that the proteins of these genes interact in a common neural network. Therefore, more attention to these genes is warranted in genetic studies of patients with neurodevelopmental disorders, particularly ASD.

Algunos problemas en la investigación para el control de la transmisión de Ochocerca volvulus en México / Research for the control of the transmission of Onchocerca volvulus in Mexico

El tratamiento y control de la oncocercosis en México ha sustentado desde su inicio en la eliminación de las microfilarias con el uso de la dietilcarbamazina y la extirpación quirúrgica de los oncocercomas que arrojan los gusanos adultos. Estas medidas al parecer han disminuido la prevalencia e incidencia de la ceguera en aquellos individuos afectados por esa parasitosis. Sin embargo, no se ha logrado un impacto importante sobre la transmisión de la oncocercosis en México el control químico del vector ha tenido buenos resultados en otras regiones del mundo; en México, sin embargo no ha sido plenamente aceptado como parte integral del control de la oncocercosis por diversas causas. Más aún, pocas investigaciones se han realizado en relación a la búsqueda de nuevas alternativas para el control del vector. Recientemente, el resultado de investigaciones sobre la invermectina (agente microfilaricida) mostraron que esta droga es eficaz y segura para el tratamiento de la oncocercosis. En otros reportes se ha señalado tambien que la ivermectina tiene un efecto sobre la transmisión de esta filaria. No obstante, existen algunas interrogantes acerca de su capacidad para suspender la transmisión de la oncocercosis, discutiendo los problemas para su diagnóstico, tratamiento y control. Además se propone el empleo de parámetros para la evaluación correcta de las medidas de control, con énfasis en las determinaciones entomológicas

The treatment and control of onchocerciasis in Mexico has been supported only on the administration of diethy carbamazine and the removal of adult worms, which are in the onchocercomata. These actions seems to have diminished the prevalence and incidence of blindness in those individuals who are affected by this parasitosis. However, there has not been an important impact on onchocerciasis transmission. The objective of this paper is to critically analyze and discuss subjects related to diagnosis, treatment and control of onchocerciasis transmission in Mexico. Chemical vector control has been successfully archieved in other world regions; however, in Mexico, it has not been fully acepted as part of the integral onchocerciasis control due to several causes. Moreover, there has been few scientific research activties toward the search of new options for vector control. Recently, results of research on ivermectin (a microfilaricide agent) have indicated that this drug is effective and safe for the treatment of onchocerciasis. Additionally, it has been reported that ivermectin has an effect on the onchocerciasis transmission. However, there are several unanswered questions about the efficacy of ivermectin in toping onchocerciasis transmission. In this report, the ain efforts carried out in Mexico against onchocerciasis are analysed and problems related with diagnosis, treatment and control are also discussed Some parameters for the correct evaluation of onchocerciasis control, with entomological emphasis, are proposed.