Dehydrins protect plant proteins and membranes from damage during drought and cold. Vitis riparia K 2 is a 48-residue protein that can protect lactate dehydrogenase from freeze-thaw damage by preventing the aggregation and denaturation of the enzyme. To further elucidate its mechanism, we used a series of V. riparia K 2 concatemers (K 4 , K 6 , K 8 , and K 10 ) and natural dehydrins (V. riparia YSK 2 , 60 kilodalton peach dehydrin [PCA60], barley dehydrin5 [Dhn5], Thellungiella salsuginea dehydrin2 , and Opuntia streptacantha dehydrin1 ) to test the effect of the number of K-segments and dehydrin size on their ability to protect lactate dehydrogenase from freeze-thaw damage. The results show that the larger the hydrodynamic radius of the dehydrin, the more effective the cryoprotection. A similar trend is observed with polyethylene glycol, which would suggest that the protection is simply a nonspecific volume exclusion effect that can be manifested by any protein. However, structured proteins of a similar range of sizes did not show the same pattern and level of cryoprotection. Our results suggest that with respect to enzyme protection, dehydrins function primarily as molecular shields and that their intrinsic disorder is required for them to be an effective cryoprotectant. Lastly, we show that the cryoprotection by a dehydrin is not due to any antifreeze proteinlike activity, as has been reported previously.

The COVID-19 pandemic has led to the rapid adoption of virtual clinic processes and healthcare delivery. Herein, we examine the impact of virtualising genetics services at Canada’s largest cancer centre. A retrospective review was conducted to evaluate relevant metrics during the 12 weeks prior to and during virtual care, including referral and clinic volumes, patient wait times and genetic testing uptake. The number of appointments and new patients seen were maintained during virtual care. Likewise, there was a significant increase in the number of patients offered testing during virtual care who did not provide a blood sample (176/180 (97.7%) vs 180/243 (74.1%); p<0.001), and a longer median time from the date of pretest genetic counselling to the date a sample was given (0 vs 11 days; p<0.001). Referral volumes significantly decreased during virtual care (35 vs 22; p<0.001), which was accompanied by a decreased median wait time for first appointment (55 days vs 30 days; p<0.001). The rapid virtualisation of cancer genetic services allowed the genetics clinic to navigate the COVID-19 pandemic without compromising clinical volumes or access to genetic testing. There was a decrease in referral volumes and uptake of genetic testing, which may be attributable to pandemic-related clinical restrictions.

KBG syndrome is a rare autosomal dominant genetic condition characterized by neurological involvement and distinct facial, hand, and skeletal features. More than 70 cases have been reported; however, it is likely that KBG syndrome is underdiagnosed because of lack of comprehensive characterization of the heterogeneous phenotypic features. We describe the clinical manifestations in a male currently 13 years of age, who exhibited symptoms including epilepsy, severe developmental delay, distinct facial features, and hand anomalies, without a positive genetic diagnosis. Subsequent exome sequencing identified a novel de novo heterozygous single base pair duplication (c.6015dupA) in ANKRD11, which was validated by Sanger sequencing. This single-nucleotide duplication is predicted to lead to a premature stop codon and loss of function in ANKRD11, thereby implicating it as contributing to the proband's symptoms and yielding a molecular diagnosis of KBG syndrome. Before molecular diagnosis, this syndrome was not recognized in the proband, as several key features of the disorder were mild and were not recognized by clinicians, further supporting the concept of variable expressivity in many disorders. Although a diagnosis of cerebral folate deficiency has also been given, its significance for the proband's condition remains uncertain.

5543 Background: High grade serous ovarian cancers (HGSC) with BRCA mutation are biologically unique, with distinct molecular and clinical behaviour from sporadic cases. It is unclear if these biological differences translate to favorable outcomes at the time of primary cytoreductive surgery (PCS). The aim of this study is to compare the amount of residual disease following PCS in BRCA-mutated (BRCAm) and wildtype (BRCAwt) HGSC, and to assess whether BRCA status is an independent predictor of residual disease. Methods: We conducted a retrospective analysis of patients with HGSC with known germline and somatic BRCA mutation status, treated with PCS from 2000 to 2017. We compared the cytoreduction outcomes between the BRCAm and the BRCAwt cohorts and built a predictive model to assess whether BRCA status was associated with amount of residual disease at the time of PCS. Results: Of 355 women, 144 harbored germline or somatic BRCA mutations (41%) and 211 were BRCAwt (59%). BRCAm women tended to be younger (54 vs. 59; p < 0.001), but there were no differences between the two groups in stage, disease burden at presentation, surgical complexity score, length of surgery, or perioperative complications. The BRCAm group had a higher rate of complete cytoreduction to no residual disease (0mm) [75% vs. 54%], and a lower rate of optimal cytoreduction (1-9mm) [16% vs. 34%] or suboptimal cytoreduction (≥10mm) [9% vs. 12%] (p < 0.001). In our predictive model, after accounting for length of surgery, CA-125 level, stage, disease scores and surgical complexity scores, BRCAm status was predictive of complete cytoreduction to 0mm residual disease (OR 4.78; 95% CI 2.32-9.85; p < 0.001). Conclusions: BRCA status is predictive of complete cytoreduction at time of PCS in HGSC. Timely availability of BRCA testing is paramount as it may aid in the therapeutic decision making between PCS or neoadjuvant chemotherapy in women with newly diagnosed HGSC.