Mayo Test Catalog, (Sorted By Test Name) - Mayo Medical ...

ACVK
89393
(see Table).
Useful For: The definitive evaluation of an individual with JAK2-negative erythrocytosis associated
with lifelong sustained increased RBC mass, elevated RBC count, hemoglobin, or hematocrit
Interpretation: An interpretive report will be provided and will include specimen information, assay
information, and whether the specimen was positive for any mutations in the gene. If positive, the
mutation will be correlated with clinical significance, if known.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Patnaik MM, Tefferi A: The complete evaluation of erythrocytosis:
congenital and acquired. Leukemia 2009 May;23(5):834-844 2. McMullin MF: The classification and
diagnosis of erythrocytosis. Int J Lab Hematol 2008;30:447-459 3. Percy MJ, Lee FS: Familial
erythrocytosis: molecular links to red blood cell control. Haematologica 2008 Jul;93(7):963-967 4.
Huang LJ, Shen YM, Bulut GB: Advances in understanding the pathogenesis of primary familial and
congenital polycythaemia. Br J Haematol 2010 Mar;148(6):844-852 5. Maran J, Prchal J: Polycythemia
and oxygen sensing. Pathologie Biologie 2004;52:280-284 6. Lee F: Genetic causes of erythrocytosis
and the oxygen-sensing pathway. Blood Rev 2008;22:321-332 7. Merchant SH, Oliveira JL, Hoyer JD,
Viswanatha DS: Erythrocytosis. In Hematopathology. Second edition. Edited by ED His. Philadelphia,
Elsevier Saunders, 2012, pp 22-723 8. Zhuang Z, Yang C, Lorenzo F, et al: Somatic HIF2A
gain-of-function mutations in paraganglioma with polycythemia. N Engl J Med 2012 Sep
6;367(10):922-930
Hereditary Hemorrhagic Telangiectasia, ACVRL1 Gene, Known
Mutation
Clinical Information: Hereditary hemorrhagic telangiectasia (HHT), also known as
Osler-Weber-Rendu syndrome, is an autosomal dominant vascular dysplasia characterized by the
presence of arteriovenous malformations (AVMs) of the skin, mucosa, and viscera. Small AVMs, or
telangiectasias, develop predominantly on the face, oral cavity, and/or hands, and spontaneous,
recurrent epistaxis (nosebleeding) is a common presenting sign. Symptomatic telangiectasias occur in
the gastrointestinal tract of about 30% of HHT patients. Additional serious complications associated
with HHT include transient ischemic attacks, embolic stroke, heart failure, cerebral abscess, massive
hemoptysis, massive hemothorax, seizure, and cerebral hemorrhage. These complications are a result of
larger AVMs, which are most commonly pulmonary, hepatic, or cerebral in origin, and occur in
approximately 30%, 40%, and 10% of individuals with HHT, respectively. HHT is inherited in an
autosomal dominant manner; most individuals have an affected parent. HHT occurs with wide ethnic
and geographic distribution, and it is significantly more frequent than formerly thought. It is most
common in Caucasians, but it occasionally occurs in Asians, Africans, and individuals of Middle
Eastern descent. The overall incidence of HHT in North America is estimated to be between 1:5,000
and 1:10,000. Penetrance seems to be age related, with increased manifestations occurring over
oneâ€s lifetime. For example, approximately 50% of diagnosed individuals report having nosebleeds
by age 10 years, and 80% to 90% by age 21 years. As many as 90% to 95% of affected individuals
eventually develop recurrent epistaxis. Two genes are most commonly associated with HHT: the
endoglin gene (ENG), containing 15 exons and located on chromosome 9 at band q34; and the activin A
receptor, type II-like 1 gene (ACVRL1 or ALK1), containing 10 exons and located on chromosome 12
at band q1. Mutations in these genes occur in about 80% of individuals with HHT. ENG and ACVRL1
encode for membrane glycoproteins involved in transforming growth factor-beta signaling related to
vascular integrity. Mutations in ENG are associated with HHT type 1 (HHT1), which has been reported
to have a higher incidence of pulmonary AVMs, whereas ACVRL1 mutations occur in HHT type 2
(HHT2), which has been reported to have a higher incidence of hepatic AVMs. It has been suggested
that HHT1 has a more severe phenotype compared to HHT2. ACVRL1 gene, known mutation testing is
for the genetic testing of individuals who are at risk for an ACVRL1 mutation that has been previously
identified in the family. If the familial mutation is not known, the familial proband should be screened
for ENG and ACVRL1 mutations via full gene analyses (ACVK/89394 Hereditary Hemorrhagic
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