“TWO FOR ONE”, NOVEL DUAL LAD VARIANT: TYPE XIII

dbVar houses over 3 million submitted structural variants (SSV) from 120 human studies including copy number variations (CNV), insertions, deletions, inversions, translocations, and complex chromosomal rearrangements. Users can submit multiple SSVs to dbVAR that are presumably identical, but were ascertained by different platforms and samples, to calculate whether the variant is rare or common in the population and allow for cross validation. However, because SSV genomic location reporting can vary – including fuzzy locations where the start and/or end points are not precisely known – analysis, comparison, annotation, and reporting of SSVs across studies can be difficult. This project was initiated by the Structural Variant Comparison Group for the purpose of generating a non-redundant set of genomic regions defined by counts of concordance for all human SSVs placed on RefSeq assembly GRCh38 (RefSeq accession GCF_000001405.26). We intend that the availability of these regions, called structural variant clusters (SVCs), will facilitate the analysis, annotation, and exchange of SV data and allow for simplified display in genomic sequence viewers for improved variant interpretation. Sets of SVCs were generated by variant type for each of the 120 studies as well as for a combined set across all studies. Starting from 3.64 million SSVs, 2.5 million and 3.4 million non-redundant SVCs with count >=1 were generated by variant type for each study and across all studies, respectively. In addition, we have developed utilities for annotating, searching, and filtering SVC data in GVF format for computing summary statistics, exporting data for genomic viewers, and annotating the SVC using external data sources.

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Protein Truncating Variants of colA in Clostridium perfringens Type G Strains

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.645248 ◽

2021 ◽

Vol 11 ◽

Author(s):

Lore Van Damme ◽

Natasja Cox ◽

Chana Callens ◽

Michelle Dargatz ◽

Monika Flügel ◽

...

Keyword(s):

Clostridium Perfringens ◽

Collagen Type ◽

Gelatin Zymography ◽

Relative Activity ◽

Full Length ◽

Collagen Type Iv ◽

Type I ◽

Necrotic Enteritis ◽

Variant Type ◽

Type Iv

Extracellular matrix (ECM) degrading enzymes produced by Clostridium perfringens may play an important role during the initial phases of avian necrotic enteritis by facilitating toxin entry in the intestinal mucosa and destruction of the tissue. C. perfringens is known to produce several ECM-degrading proteases, such as kappa toxin, an extracellular collagenase that is encoded by the colA gene. In this study, the colA gene sequence of a collection of 48 C. perfringens strains, including pathogenic (i.e. toxinotype G) and commensal (i.e. toxinotype A) chicken derived strains and strains originating from other host species, was analyzed. Although the colA gene showed a high level of conservation (>96% nucleotide sequence identity), several gene variants carrying different nonsense mutations in the colA gene were identified, leading to the definition of four truncated collagenase variant types (I-IV). Collagenase variant types I, III and IV have a (nearly) complete collagenase unit but lack parts of the C-terminal recruitment domains, whereas collagenase variant types II misses the N-terminal part of collagenase unit. Gene fragments encoding a truncated collagenase were mainly linked with necrotic enteritis associated C. perfringens type G strains with collagenase variant types I and II being the most prevalent types. Gelatin zymography revealed that both recombinant full-length and variant type I collagenase have active auto-cleavage products. Moreover, both recombinant fragments were capable of degrading type I as well as type IV collagen, although variant type I collagenase showed a higher relative activity against collagen type IV as compared to full-length collagenase. Consequently, these smaller truncated collagenases might be able to break down collagen type IV in the epithelial basement membrane of the intestinal villi and so contribute to the initiation of the pathological process leading to necrotic enteritis.

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Pan-nephritis (glomerulonephritis, arteriolitis, and tubulointerstitial nephritis) associated with predominant mesangial C1q deposition and hypocomplementemia: a variant type of C1q nephropathy?

American Journal of Kidney Diseases ◽

10.1016/s0272-6386(96)90171-7 ◽

1996 ◽

Vol 27 (4) ◽

pp. 583-587 ◽

Cited By ~ 6

Author(s):

Hirokazu Imai ◽

Tadashi Yasuda ◽

Ken Satoh ◽

Akira B. Miura ◽

Tamotsu Sugawara ◽

...

Keyword(s):

Tubulointerstitial Nephritis ◽

C1q Nephropathy ◽

Variant Type

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SMAD3 pathogenic variants: risk for thoracic aortic disease and associated complications from the Montalcino Aortic Consortium

Journal of Medical Genetics ◽

10.1136/jmedgenet-2018-105583 ◽

2019 ◽

Vol 56 (4) ◽

pp. 252-260 ◽

Cited By ~ 14

Author(s):

Ellen M Hostetler ◽

Ellen S Regalado ◽

Dong-Chuan Guo ◽

Nadine Hanna ◽

Pauline Arnaud ◽

...

Keyword(s):

Age Of Onset ◽

Cumulative Risk ◽

Aortic Disease ◽

Aortic Aneurysms ◽

Thoracic Aortic Disease ◽

Thoracic Aortic Aneurysms ◽

Missense Variants ◽

Variant Type ◽

Pathogenic Variants ◽

Reduced Penetrance

BackgroundPathogenic variants in SMAD3 cause thoracic aortic aneurysms and dissections, along with aneurysms and rupture of other arteries. Here, we examined differences in clinical presentation of aortic events (dissection or surgical repair of an aneurysm) with respect to age and variant type in an international cohort of individuals with SMAD3 variants.MethodsAortic status and events, vital status and clinical features were abstracted through retrospective review of medical records of 212 individuals with 51 unique SMAD3 variants, including haploinsufficiency (HI) and missense substitutions in the MH2 domain, as well as novel in-frame deletions and missense variants in the MH1 domain.ResultsAortic events were documented in 37% of cases, with dissections accounting for 70% of events. The median age at first aortic event was significantly lower in individuals with SMAD3 MH2 missense variants than those with HI variants (42years vs 49 years; p=0.003), but there was no difference in frequency of aortic events by variant type. The cumulative risk of an aortic event was 50% at 54 years of age. No aortic events in childhood were observed.ConclusionsSMAD3 pathogenic variants cause thoracic aortic aneurysms and dissections in the majority of individuals with variable age of onset and reduced penetrance. Of the covariates examined, the type of underlying SMAD3 variant was responsible for some of this variation. Later onset of aortic events and the absence of aortic events in children associated with SMAD3 variants support gene-specific management of this disorder.

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