Factor XI deficiency; Rosenthal disease; PTA deficiency - F11 gene
Factor XI deficiency, also known as Rosenthal disease or PTA deficiency, is a process associated with bleeding problems. The most frequent characteristic of factor XI deficiency is prolonged bleeding after trauma or surgery, especially of the oral and nasal cavities or the urinary tract. Other signs and symptoms may include frequent nosebleeds, easy development of bruises, subcutaneous and gum bleedings; or menorrhagia in women. Muscle or joint hemorrhages, which can cause long-term disability in other disorders related to coagulation problems, usually do not occur in this process.
This process is due in most cases to mutations in the F11 gene (coagulation factor XI), located on the long arm of chromosome 4 (4q35.2), which encodes the factor XI protein. This protein plays a role in the coagulation process. Factor XI is synthesized mainly by the liver cells. The protein circulates in the bloodstream and normally remains inactive until the coagulation process is activated after an injury that damages the blood vessels.
At least 250 mutations in the F11 gene have been identified in individuals with factor XI deficiency. The mutations identified reduce the amount of factor XI in the bloodstream or result in the synthesis of a factor XI protein with impaired function. A deficiency of functional factor XI slows down blood clotting, which results in episodes of bleeding. The severity of bleeding problems in affected individuals does not necessarily correspond to the amount of factor XI in the bloodstream, and may vary even within the same family. Other genetic and environmental factors probably play a role in determining severity.
In some affected individuals, mutations in the F11 gene have not been identified. In these cases the process is known as factor XI acquired deficiency and can develop as part of other processes in which the immune system does not act correctly and attacks the factor XI protein or is a result of liver disease. In addition, approximately 25% of people with Noonan syndrome are deficient in factor XI.
This disease is most often inherited with an autosomal recessive pattern, which means that both copies of the gene in each cell must have the mutations for the alteration to be expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually do not show signs and symptoms of the disease. Cases of autosomal dominant inheritance have been described, which means that a copy of the altered F11 gene in each cell is sufficient to express the process. In these cases, an affected person has an affected parent.
Tests performed in IVAMI: in IVAMI we perform the detection of mutations associated with factor XI deficiency, by means of complete PCR amplification of the exons of the F11 gene, and their subsequent sequencing.
Recommended samples: blood drawn with EDTA for separation of blood leukocytes, or card impregnated with dried blood sample (IVAMI can mail the card to deposit the blood sample).