Siblings with Rare Hemophilia a Genetic Mutation and Normal Factor VIII Levels

CONCLUSIONThe c.1621A>T (p.Thr541Ser) variant which occurs in exon 11 of the FVIII gene, has been is known to cause mild hemophilia A. The Thr541Ser substitution is rare and is present in ~0.009% of the NHLBI exome sequencing project. This is a unique case series of siblings with a rare mutation having normal Factor VIII levels and grandfather with similar mutation who was eventually also diagnosed with mild hemophilia A. The underlying gene mutation is an important but not sole determinant of residual FVIII:C in hemophilia A patients. As our understanding of pathophysiologic process of causative genetic event and baseline FVIII:C in patients is limited, this case series highlights the current diagnostic challenges in the mild Hemophilia A population and the importance of appropriate diagnostic techniques to avoid delayed diagnosis. Correct identification of mutations also provides the opportunity to define molecular consequences and identify residues important for factor VIII activity.DisclosuresCarpenter: Bayer: Honoraria; Kedrion Biopharmaceuticals: Consultancy; Nationwide Children's Hospital: Speakers Bureau; Kane County State's Attorney: Consultancy; 4th Judicial District Attorney's Office- Colorado: Consultancy; Kedrion Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; HEMA Biologics: Consultancy; CSL Behring: Speakers Bureau; National Hemophilia Foundation (Impact Education): Speakers Bureau; Genentech Incorporated: Membership on ...
Source: Blood - Category: Hematology Authors: Tags: 321. Blood Coagulation and Fibrinolytic Factors Source Type: research