scholarly journals Biochemical and structural characterization of two variants of uncertain significance in the PMS2 gene

2019 ◽  
Vol 40 (4) ◽  
pp. 458-471 ◽  
Author(s):  
Brandon M. D'Arcy ◽  
Jessa Blount ◽  
Aishwarya Prakash
Keyword(s):  
Structural Characterization ◽  
Variants Of Uncertain Significance ◽  
Uncertain Significance ◽  
Pms2 Gene

scholarly journals Functional CDKN2A assay identifies frequent deleterious alleles misclassified as variants of uncertain significance

eLife ◽  
2022 ◽  
Vol 11 ◽  
Author(s):  
Hirokazu Kimura ◽  
Raymond M Paranal ◽  
Neha Nanda ◽  
Laura D Wood ◽  
James R Eshleman ◽  
...  
Keyword(s):  
Functional Characterization ◽  
Ductal Adenocarcinoma ◽  
Proliferation Assay ◽  
Variants Of Uncertain Significance ◽  
Pathogenic Variants ◽  
Deleterious Alleles ◽  
Increased Risk ◽  
Uncertain Significance

Pathogenic germline CDKN2A variants are associated with an increased risk of pancreatic ductal adenocarcinoma (PDAC). CDKN2A variants of uncertain significance (VUSs) are reported in up to 4.3% of patients with PDAC and result in significant uncertainty for patients and their family members as an unknown fraction are functionally deleterious, and therefore, likely pathogenic. Functional characterization of CDKN2A VUSs is needed to reclassify variants and inform clinical management. 29 germline CDKN2A VUSs previously reported in patients with PDAC or in ClinVar were evaluated using a validated in vitro cell proliferation assay. 12 of the 29 CDKN2A VUSs were functionally deleterious (11 VUSs) or potentially functionally deleterious (1 VUS) and were reclassified as likely pathogenic variants. Thus, over 40% of CDKN2A VUSs identified in patients with PDAC are functionally deleterious and likely pathogenic. When incorporating VUSs found to be functionally deleterious, and reclassified as likely pathogenic, the prevalence of pathogenic/likely pathogenic CDKN2A in patients with PDAC reported in the published literature is increased to up to 4.1% of patients, depending on family history. Therefore, CDKN2A VUSs may play a significant, unappreciated role in risk of pancreatic cancer. These findings have significant implications for the counselling and care of patients and their relatives.

scholarly journals Characterization of BRCA1 ring finger variants of uncertain significance

2009 ◽  
Vol 119 (3) ◽  
pp. 737-743 ◽  
Author(s):  
Kevin Sweet ◽  
Leigha Senter ◽  
Robert Pilarski ◽  
Lai Wei ◽  
Amanda Ewart Toland
Keyword(s):  
Ring Finger ◽  
Variants Of Uncertain Significance ◽  
Uncertain Significance

scholarly journals Functional characterization of 84 PALB2 variants of uncertain significance

2019 ◽  
Vol 22 (3) ◽  
pp. 622-632 ◽  
Author(s):  
Timothy Wiltshire ◽  
Mandy Ducy ◽  
Tzeh Keong Foo ◽  
Chunling Hu ◽  
Kun Y. Lee ◽  
...  
Keyword(s):  
Functional Characterization ◽  
Variants Of Uncertain Significance ◽  
Uncertain Significance

New ultrastructural findings about Borrelia burgdorferi by cryofixation, negative staining, thin sectioning and scanning techniques

1990 ◽  
Vol 48 (3) ◽  
pp. 582-583
Author(s):  
S. F. Hayes ◽  
M. D. Corwin ◽  
T. G. Schwan ◽  
D. W. Dorward ◽  
W. Burgdorfer
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Structural Characterization ◽  
Negative Staining ◽  
Low Speed ◽  
Thin Sectioning ◽  
Ultrastructural Findings

Characterization of Borrelia burgdorferi strains by means of negative staining EM has become an integral part of many studies related to the biology of the Lyme disease organism. However, relying solely upon negative staining to compare new isolates with prototype B31 or other borreliae is often unsatisfactory. To obtain more satisfactory results, we have relied upon a correlative approach encompassing a variety EM techniques, i.e., scanning for topographical features and cryotomy, negative staining and thin sectioning to provide a more complete structural characterization of B. burgdorferi.For characterization, isolates of B. burgdorferi were cultured in BSK II media from which they were removed by low speed centrifugation. The sedimented borrelia were carefully resuspended in stabilizing buffer so as to preserve their features for scanning and negative staining. Alternatively, others were prepared for conventional thin sectioning and for cryotomy using modified procedures. For thin sectioning, the fixative described by Ito, et al.

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