Background Rare diseases are pathologies that affect less than 1 in 2000 people. They are difficult to diagnose due to their low frequency and their often highly heterogeneous symptoms. Rare diseases have in general a high impact on the quality of life and life expectancy of patients, which are in general children or young people. The advent of high-throughput sequencing techniques has improved diagnosis in several different areas, from pediatrics, achieving a diagnostic rate of 41% with whole genome sequencing (WGS) and 36% with whole exome sequencing, to neurology, achieving a diagnostic rate between 47 and 48.5% with WGS. This evidence has encouraged our group to pursue a molecular diagnosis using WGS for this and several other patients with rare diseases. Results We used whole genome sequencing to achieve a molecular diagnosis of a 7-year-old girl with a severe panvascular artery disease that remained for several years undiagnosed. We found a frameshift variant in one copy and a large deletion involving two exons in the other copy of a gene called YY1AP1. This gene is related to Grange syndrome, a recessive rare disease, whose symptoms include stenosis or occlusion of multiple arteries, congenital heart defects, brachydactyly, syndactyly, bone fragility, and learning disabilities. Bioinformatic analyses propose these mutations as the most likely cause of the disease, according to its frequency, in silico predictors, conservation analyses, and effect on the protein product. Additionally, we confirmed one mutation in each parent, supporting a compound heterozygous status in the child. Conclusions In general, we think that this finding can contribute to the use of whole genome sequencing as a diagnosis tool of rare diseases, and in particular, it can enhance the set of known mutations associated with different diseases.

The objective of this study was to test the effect of the combined application of lactic acid (0–5%) (LA) and UV-C light (0–330 mJ/cm2) to reduce Listeria monocytogenes and lactic acid bacteria (LAB) on beef without major meat color (L *, a *, b *) change and its impact over time. A two-factor central composite design with five central points and response surface methodology (RSM) were used to optimize LA concentration and UV-C dose using 21 meat pieces (10 g) inoculated with L. monocytogenes (LM100A1). The optimal conditions were analyzed over 8 weeks. A quadratic model was obtained that predicted the L. monocytogenes log reduction in vacuum-packed beef treated with LA and UV-C. The maximum log reduction for L. monocytogenes (1.55 ± 0.41 log CFU/g) and LAB (1.55 ± 1.15 log CFU/g) with minimal impact on meat color was achieved with 2.6% LA and 330 mJ/cm2 UV-C. These conditions impaired L. monocytogenes growth and delayed LAB growth by 2 weeks in vacuum-packed meat samples throughout 8 weeks at 4 °C. This strategy might contribute to improving the safety and shelf life of vacuum-packed beef with a low impact on meat color.

Specific diagnosis of many genetic diseases is challenging. One area where greater difficulties are met is that of developmental disorders of the central nervous system, since many genes can be involved (van Loo & Martens, 2007) with many more to be discovered probably. In more broad terms, rare diseases (RD) are pathologies that affect less than 1 in 2000 people (Commission & -European Commission, 2020). Due to their low frequency, they present diverse difficulties, from the delay in the diagnosis to the lack of specific treatments. Most of them have a

ResumenEl objetivo de este trabajo fue determinar la vida útil de cortes cárnicos envasados al vacío y almacenados a 0°C y 4°C. Se evaluaron parámetros fisicoquímicos (pH, porcentaje de Drip, rancidez por Kreiss), aspecto del corte (estado del envase, color del corte, grasa, olor); y aspectos microbiológicos (recuentos en placa de bacterias aerobias mesófilas, enterobacterias, Escherichia coli, coliformes totales, bacterias ácido lácticas) en cortes de bife y picaña durante 5 meses.En los cortes almacenados a 4°C se observaron alteraciones fisicoquímicas y de aspecto en el tercer mes (pH <5.4, perdida de vacío y presencia de olores ácidos); mientras que a 0°C no se percibieron alteraciones hasta el quinto mes. Por otro lado, no se observó crecimiento significativo para E.coli ni coliformes totales durante el periodo en estudio.El almacenamiento de cortes envasados al vacío y mantenidos a 0°C contribuye a la calidad del producto, y mantiene sus características fisicoquímicas y sensoriales en condiciones comercialmente aceptables durante cuatro meses, permitiendo su transporte hasta destinos distantes. Palabras clave: envasado al vacío, vida útil, carnes envasadas AbstractThe aim of this work was to determine the shelf life of vacuum-packed eat cuts and stored to 0ºC and 4ºC. There were evaluated physicochemical parameters (pH, Drip percentage, rancidity by Kreiss), cut appearance (state of container, color of the cut, fat, smell); and microbiological aspects (Plate counts of aerobic mesophilic bacteria, enterobacteriaceace, Escherichia coli, total coliforms, lactic acid bacteria) in cuts of beef and cattle prod during 5 months.In the cuts stored at 4ºC, there were observed psychochemical and appearance changes during the third month (pH <5.4, loss of vacuum and existence of sour odor); whereas at 0ºC, there were not perceived changes until the fifth month. On the other hand, there was not observed any meaningful growth neither to E. coli nor to the total coliforms during the study period.The storage of vacuum-packed cuts and kept at 0ºC contributes to the quality of the product, and keeps its psychochemical and sensory features in commercially acceptable conditions during four months, allowing its shipping to away destinations.

The SPATA5 gene encodes a 892 amino-acids long protein that has a putative mitochondrial targeting sequence and has been proposed to function in maintenance of mitochondrial function and integrity during mouse spermatogenesis. Several studies have associated homozygous or compound heterozygous mutations in SPATA5 gene to microcephaly, intellectual disability, seizures and hearing loss. This suggests a role of the SPATA5 gene also in neuronal development. Recently, our group presented results validating the use of blood cells for the assessment of mitochondrial function for diagnosis and follow-up of mitochondrial disease, minimizing the need for invasive procedures such as muscle biopsy. In this study, we were able to diagnose a patient with epileptogenic encephalopathy using next generation sequencing. We found two novel compound heterozygous variants in SPATA5 that are most likely causative. To analyze the impact of SPATA5 mutations on mitochondrial functional studies directly on the patients' mononuclear cells and platelets were undertaken. Oxygen consumption rates in platelets and PBMCs were impaired in the patient when compared to a healthy control. Also, a decrease in mitochondrial mass was observed in the patient monocytes with respect to the control. This suggests a true pathogenic effect of the mutations in mitochondrial function, especially in energy production and possibly biogenesis, leading to the observed phenotype.