Arthrogryposis is a clinical finding that is present either as a feature of a neuromuscular condition or as part of a systemic disease in over 400 Mendelian conditions. The underlying molecular etiology remains largely unknown because of genetic and phenotypic heterogeneity. We applied exome sequencing (ES) in a cohort of 89 families with the clinical sign of arthrogryposis. Additional molecular techniques including array comparative genomic hybridization (aCGH) and Droplet Digital PCR (ddPCR) were performed on individuals who were found to have pathogenic copy number variants (CNVs) and mosaicism, respectively. A molecular diagnosis was established in 65.2% (58/89) of families. Eleven out of 58 families (19.0%) showed evidence for potential involvement of pathogenic variation at more than one locus, probably driven by absence of heterozygosity (AOH) burden due to identity-by-descent (IBD). RYR3, MYOM2, ERGIC1, SPTBN4, and ABCA7 represent genes, identified in two or more families, for which mutations are probably causative for arthrogryposis. We also provide evidence for the involvement of CNVs in the etiology of arthrogryposis and for the idea that both mono-allelic and bi-allelic variants in the same gene cause either similar or distinct syndromes. We were able to identify the molecular etiology in nine out of 20 families who underwent reanalysis. In summary, our data from family-based ES further delineate the molecular etiology of arthrogryposis, yielded several candidate disease-associated genes, and provide evidence for mutational burden in a biological pathway or network. Our study also highlights the importance of reanalysis of individuals with unsolved diagnoses in conjunction with sequencing extended family members.

Although multiple nerve enlargements at typical entrapment sites on sonographic evaluation can suggest HNPP, ultrasonography cannot be used as a diagnostic tool for HNPP. Ultrasonography may contribute to the differential diagnosis of HNPP and other demyelinating polyneuropathies or compression neuropathies; however, further studies are required.

1. The aim of the present study was to examine the effects of improving vitamin D status in broiler diets by supplementary 25-hydroxycholecalciferol (25OHD), alone or in combination with calcium (Ca) and available phosphorus (aP), on live performance, sternum mineralisation and breast meat quality in broilers. 2. A total of 936 1-d-old Ross 308 broilers were used in the study. After gender determination at the hatchery, chicks from each sex were randomly distributed into three dietary treatments. The following dietary treatments were used in the experiment from hatch to 38 d: (1) A control diet formulated to meet all of the nutrient requirements of broiler chicks according to the management guide; (2) The control diet supplemented with 18.7-15.0 µg/kg of 25OHD; and (3) The control diet supplemented with 18.7-15.0 µg/kg of 25OHD plus Ca + aP. 3. Improvement in vitamin D status by 25OHD supplementation, alone or in combination with Ca and aP, had no effect on body weight and feed conversion ratio of broilers. 4. The serum 25OHD concentration significantly increased with 25OHD and 25OHD plus Ca + aP supplementation (P < 0.05), whereas the ionised Ca and Mg concentrations remained unchanged. 5. Sternum absolute weight, ash content and the concentrations of Ca and P significantly increased (P < 0.01) with supplementation of 25OHD, alone or in combination with Ca + aP. 6. Supplemental 25OHD, alone or in combination with Ca + aP, slightly increased pH (P = 0.05) and decreased (P < 0.01) squeezable water loss in breast meat, whereas it had no significant effect on lightness, yellowness and sarcoplasmic protein solubility. 7. In conclusion, the results suggested that enhancing vitamin D status by 25OHD supplementation alone or in combination with Ca + aP may improve sternum structure and mineral accretion. Furthermore, supplemental 25OHD, even in a nutritionally complete diet, may offer an effective way to improve protein solubility in female broilers.

Parkinson's disease (PD) is associated with degeneration of the dopaminergic neurons in the substantia nigra. The subthalamic nucleus (STN) plays a pivotal role in the pathogenesis. However, there is not much known about the morphological changes in the STN. The red nucleus (RN) has many connections with the motor coordinating pathways although it is not primarily involved in the pathogenesis. In this study we aimed to compare the volumes of the STN and RN measured by magnetic resonance imaging in PD patients and controls to investigate how these structures are affected at the morphological level. Twenty patients with PD and twenty age/sex matched controls were enrolled in this study. Severity score was determined by Hoehn & Yahr staging: 6 at stage II and 14 at stage III in med-off state. Imaging was performed by a 1.5 Tesla (T) MR scanner. Measurements of total brain and normalized STN and RN volumes were performed by manual planimetry using Image J software. No statistically significant differences were observed between two groups based on age or gender and disease stage and nuclei volumes. The total estimated brain volumes were not different between PD patients and controls. However, normalized volumes of the STN and RN were 14% and 16% larger, respectively, in PD patients compared to the controls (p < 0.05). Our findings suggest that the volumes of the STN and RN are increased in patients with PD. These changes possibly reflect the altered metabolic activity of these regions demonstrated by neurophysiological studies.

AIM: To investigate the effect of using microelectrode recording (MER) on the length of time required to carry out a deep brain stimulation (DBS) procedure of the subthalamic nucleus in patients with Parkinson's disease (PD). MATERIAL and METHODS: The time required to include MER in the DBS operation was calculated for the first and second sides in 24 patients with PD. The number of microelectrodes used on each trajectory for the first and second sides, and the percentage of permanent electrodes implanted on each trajectory for the first and second sides, were quantified. RESULTS: The average times taken to use MER were 23.4 ± 6.2 minutes, 17.4 ± 6.5 minutes, and 41.2 ± 6.3 minutes for the first side, second side and total procedure, respectively. In 75% of patients, the permanent electrode was implanted at the planned target site for the first side, and in 61% of patients for the second side. CONCLUSION: MER extends the time required to carry out the DBS procedure. However, during surgery, it provides real-time information on the electrodes' neurophysiological locations and helps the surgical team choose an alternative target if the planned target does not produce satisfying results.