A Compound Heterozygosis of Two Novel Mutations in vWF Exacerbates vWD in a Chinese Pedigree.
Clin Lab
; 70(2)2024 Feb 01.
Article
en En
| MEDLINE
| ID: mdl-38345986
ABSTRACT
BACKGROUND:
von Willebrand disease (vWD), caused by mutations in the von Willebrand factor (vWF) coding gene, is a disease characterized by abnormal coagulation activity and a severe tendency for hemorrhage. Therefore, identifying mutations in vWF is important for diagnosing congenital vWD.METHODS:
We studied a 23-year-old male vWD patient and his parents. Clotting methods were used to determine activated partial thromboplastin time (aPTT), prothrombin time (PT), fibrinogen (FIB) levels, FVIII activity. Chromogenic substrate method was used to determine vWF antigen and activity. The platelet count was determined. Mutations were searched using whole-exome sequencing and certified by Sanger sequencing. Clinical data, including activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen levels, FX activity, FX antigen levels, and the platelet count were collected. A mixing study was performed to eliminate the presence of coagulation factor inhibitors and lupus anticoagulants. Mutations were screened by using whole-exome sequencing (WES) and were verified by using Sanger sequencing.RESULTS:
The proband showed severely decreased vWF antigen, vWF activity, and FVIII activity. RIPA (RISTO-CETIN-induced platelet aggregation) was 0%. Data from WES showed that the proband carried compound heterozygous variants vWF NM_000552.5 (c.3213C>A p.Cys1071Ter) and vWF NM_000552.5 (c.6598+2T>C). The proband's mother carried variant vWF NM_000552.5 (c.3213C>A p.Cys1071Ter) while the proband's father carried variant vWF NM_000552.5 (c.6598+2T>C). All laboratory test indexes of the proband's parents, including vWF antigen, vWF activity, and FVIII activity, were within the normal ranges.CONCLUSIONS:
We identified a compound heterozygosis with two novel mutations in vWF (c.3213C>A, c.6598+2T >C) in a family pedigree, and our results demonstrate that the compound heterozygous mutations probably exacerbate vWD.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedades de von Willebrand
/
Factor de von Willebrand
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Adult
/
Humans
/
Male
País/Región como asunto:
Asia
Idioma:
En
Revista:
Clin Lab
Asunto de la revista:
TECNICAS E PROCEDIMENTOS DE LABORATORIO
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Alemania