A novel likely pathogenetic variant p.(Cys235Arg) of the MEN1 gene in multiple endocrine neoplasia type 1 with multifocal glucagonomas.

PURPOSE: Multiple endocrine neoplasia type 1 (MEN1) is a hereditary endocrine syndrome caused by pathogenic variants in MEN1 tumor suppressor gene. Diagnosis is commonly based on clinical criteria and confirmed by genetic testing. The objective of the present study was to report on a MEN1 case characterized by multiple pancreatic glucagonomas, with particular concern on the possible predisposing genetic defects. METHODS: While conducting an extensive review of the most recent scientific evidence on the unusual glucagonoma familial forms, we analyzed the MEN1 gene in a 35-year-old female with MEN1, as well as her son and daughter, using Sanger and next-generation sequencing (NGS) approaches. We additionally explored the functional and structural consequences of the identified variant using in silico analyses. RESULTS: NGS did not show any known pathogenic variant in the tested regions. However, a new non-conservative variant in exon 4 of MEN1 gene was found in heterozygosity in the patient and in her daughter, resulting in an amino acid substitution from hydrophobic cysteine to hydrophilic arginine at c.703T > C, p.(Cys235Arg). This variant is absent from populations databases and was never reported in full papers: its characteristics, together with the high specificity of the patient's clinical phenotype, pointed toward a possible causative role. CONCLUSION: Our findings confirm the need for careful genetic analysis of patients with MEN1 and establish a likely pathogenic role for the new p.(Cys235Arg) variant, at least in the rare subset of MEN1 associated with glucagonomas.

A short-term comparison of wheat straw and poplar wood chips used as litter in tiestalls on hygiene, milk, and behavior of lactating dairy cows.

A short-term study was conducted to compare the effect of using poplar wood chips (PWC) instead of wheat straw (WS) litter in dairy cows. A total of 38 lactating Holstein cows (204 ± 119 days in milk, 26.9 ± 6.5 kg of milk yield [MY]) were housed in a tiestall farm for a 10-d trial including 5 d of adaptation followed by 5 sampling days (from d 5 to 10). Cows were divided into 2 homogeneous groups: one group was bedded with WS, and the second with PWC. Both litter materials were provided in the amount of 7 kg/stall per d. Each group was composed of 3 subgroups of 6 or 7 cows; the subgroups were physically separated along the feeding line by wooden boards. During the sampling days, fecal composition, used litter composition, and bacterial count (Clostridium spp., Salmonella spp., Escherichia coli, Lactobacillus, and total bacterial count) were analyzed by subgroup twice a day. On d 1 and from d 5 to 10, udder hygiene score and cow cleanliness score were also evaluated individually twice a day. Meanwhile MY, milk hygiene (total bacterial count [TBC], coliform bacterial count [CBC], and spore-forming units [SFU]) and quality were measured and analyzed from 9 animals per group. Moreover, individual animal behavior (body position and behavioral traits) and subgroup dry matter intake were measured on d 9 and 10. Fecal dry matter did not differ between groups, PWC had the lowest used litter moisture and N content favoring the highest clean cow frequency, but also gave rise to the greatest used litter microbial contamination. The MY, milk quality, TBC, SFU, and CBC were similar. The lying behavior frequency was similar between groups. However, the PWC group showed the lowest sleeping frequency, the highest frequency of other behaviors (including discomfort signs), and the lowest dry matter intake. However, despite this apparent reduction in cow comfort, no biologically important differences were observed in this short-term study between cows on PWC and WS in milk production or hygiene.