Abstract Number: PB0913
Meeting: ISTH 2021 Congress
Background: Type 3 of von Willebrand disease (vWD) demands two pathogenic variants (compound or homozygous) in the vWF gene. This type is associated with the most severe disease symptoms and almost total lack of von Willebrand factor in the bloodstream and, as a consequence, low FVIII value too.
The vWF gene consists of 52 exons and lies in the 12th chromosome.
Aims: We aimed to find pathogenic variants in the vWF gene, which could lead to observed symptoms.
Methods: We used the Sanger method to get sequences of vWF exons, using primers of our design for all the exons and exon-intron junctions, except for the first one. We chose 13 patients with VWF:RCo value ≤ 5% and FVIII:C≤10%, which describe vWD type 3.
Results: The deletion c.2435delC (Zhang, 1992) occurred in three patients in a homozygous state and in eight patients as a compound with another pathogenic variant (Table 1). In one case, no other disruptions were found, except for c.2435delC in a heterozygous state.
The only patient without c.2435delC had the following pathogenic variants: c.6970delG (new) in the 40th exon and c.2968-2 A>G (new) in intron before the 23rd exon (Table 1).
|Patient №||Pathogenic variant (1)||Exon number (1)||Reference (1)||Pathogenic variant (2)||Exon number (2)||Reference (2)|
|1||c.2435delC||18||Zhang, 1992||p.Arg273Trp||7||Allen, 2000|
|3||c.2435delC||18||Zhang, 1992||p.Arg1659Stop||28||Zhang, 1992|
|4||c.2435delC||18||Zhang, 1992||p.Ala2178Ser||37||Goodeve, 2007|
|5||c.2435delC||18||Zhang, 1992||p.Arg373Stop||10||Baronciani, 2000|
|6||c.2435delC||18||Zhang, 1992||p.Cys1101Arg||25||Gadisseur, 2009|
|7||c.2435delC||18||Zhang, 1992||p.Thr791Met||18||Gaucher, 1991|
Deletion c.2435delC is prevailing for type 3 of vWD in the Russian population, it was found in 12 patients out of 13. It is common in the world population, but we didn`t expect it to be that prevailing.
The patient with only heterozygous c.2435delC and no other changes could have a large heterozygous deletion, which could not be found by Sanger sequencing.
In total, we found four different missense and two nonsense variants, one in the splicing area, three deletions, and one insertion. All pathogenic variants, except for c.2435delC, occurred only once.
New (not mentioned in HGMD, EAHAD and NCBI) pathogenic variants were c.6457insA, c.6029delC, c.2968-2 A>G and c.6970delG.
To cite this abstract in AMA style:Chernetskaya D, Likhacheva E, Perina F, Pshenichnikova O, Surin V, Zozulya N. Prevailing c.2435delC and Other VWF Gene Defects in Russian Patients with von Willebrand Disease Type 3. Four New Pathogenic Variants Found [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 1). https://abstracts.isth.org/abstract/prevailing-c-2435delc-and-other-vwf-gene-defects-in-russian-patients-with-von-willebrand-disease-type-3-four-new-pathogenic-variants-found/. Accessed September 24, 2021.
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