Several genes have been implicated in Rett syndrome (RTT) in its typical and variant forms. We applied next-generation sequencing (NGS) to evaluate for mutations in known or new candidate genes in patients with variant forms of Rett or Rett-like phenotypes of unknown molecular aetiology. In the first step, we used NGS with a custom panel including MECP2, CDKL5, FOXG1, MEF2C and IQSEC2. In addition to a FOXG1 mutation in a patient with all core features of the congenital variant of RTT, we identified a missense (p.Ser240Thr) in CDKL5 in a patient who appeared to be seizure free. This missense was maternally inherited with opposite allele expression ratios in the proband and her mother. In the asymptomatic mother, the mutated copy of the CDKL5 gene was inactivated in 90% of blood cells. We also identified a premature stop codon (p.Arg926*) in IQSEC2 in a patient with a Rett-like phenotype. Finally, exome sequencing enabled us to characterize a heterozygous de novo missense (p.Val408Ala) in KCNA2 encoding the potassium channel Kv 1.2 in a girl with infantile-onset seizures variant of RTT. Our study expands the genetic heterogeneity of RTT and RTT-like phenotypes. Moreover, we report the first familial case of CDKL5-related disease.
Liveweight (LW) is a key and conventional indicator for monitoring and assessing overall animal performance and welfare, representing the progress along different physiological stages, while providing close indication of individual physical and health status. Measuring LW in practice is still, however, quite rare and infrequent under commercial sheep farming conditions, mainly because sessions are time-consuming, stressful either for the operator and the animals. A Walk-over-Weighing (WoW) system, already evaluated with other breeds under different conditions, was tested in this experiment lasting 14 weeks (i.e. 3 for acclimation and adaptation and 11 for data collection). We validated its use for routine and frequent monitoring the growth rate in post-weaned Merinos d'Arles ewe lambs, reared under Mediterranean grazing conditions. Similarly to previous work, the necessity for an initial adaptation period of the animals as well as for an essential data cleaning procedure of the raw database automatically collected by the WoW, were corroborated. Adaptation of naive ewe lambs enabled the required voluntary passages across the weigh platform and a high volume of individual and daily data after 2-3 weeks. Close monitoring of individual growth was then possible after performing sound data cleanings. A strong concordance of WoW LW data with the gold standard (a standard static scale) LW reference data was demonstrated. At the individual level, even with the lowest number of LW values collected with WoW, it was possible to monitor variations in LW at daily intervals. The establishment of an early warning system to help farmer decision making could therefore be possible. Our results show interesting perspectives for more precise and frequent monitoring of LW in grazing sheep without human intervention, compared to what is currently carried out on commercial farms.
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