Test ID: ACVK
Hereditary Hemorrhagic Telangiectasia, ACVRL1 Gene, Known Mutation
Secondary ID 
A test code used for billing and in test definitions created prior to November 2011
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Useful For Suggests clinical disorders or settings where the test may be helpful
Genetic testing of individuals at risk for a known activin A receptor, type II-like 1 (ACVRL1) familial mutation (associated with hereditary hemorrhagic telangiectasia)
Profile Information A profile is a group of laboratory tests that are ordered and performed together under a single Mayo Test ID. Profile information lists the test performed, inclusive of the test fee, when a profile is ordered and includes reporting names and individual availability.
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| ACVKM | ACVRL1 Gene, Known Mutation | No | Yes |
| ACVKQ | ACVRL1 Known Mutation Sequencing | No | Yes |
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Method Name A short description of the method used to perform the test
Polymerase Chain Reaction (PCR) Followed by DNA Sequence Analysis
(PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Aliases Lists additional common names for a test, as an aid in searching
ACVRL1 Gene
ALK1 Gene
Arteriovenous Malformations (AVM)
AVM (Arteriovenous Malformations)
Hereditary Hemorrhagic Telangiectasia (HHT)
HHT (Hereditary Hemorrhagic Telangiectasia)
ORW (Osler-Rendu-Weber) Disease
Osler-Rendu-Weber (ORW) Disease
Osler-Weber-Rendu (OWR) Disease
OWR (Osler-Weber-Rendu) Disease
Telangiectasia
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
This test is only applicable if a mutation has previously been identified in a family member of this individual.
Multiple cardiovascular-related gene sequencing tests can be performed on a single specimen after a single extraction. See Multiple Cardiovascular-Related Gene Sequencing Tests in Special Instructions for a list of tests that can be ordered together.
Container/Tube: Lavender top (EDTA)
Specimen Volume: 3 mL
Collection Instructions: Send specimen in original tube.
Additional Information:
1. Include physician name and phone number with the specimen.
2. Transfusions will interfere with testing for up to 4 to 6 weeks. DNA obtained from white cells may not provide useful information for patients who received a recent transfusion of blood that was not leukocyte-reduced. Wait 4 to 6 weeks until transfused cells have left the patient's circulation before drawing the patient's blood specimen for genotype testing.
Forms:
1. Hereditary Hemorrhagic Telangiectasia (HHT) Gene Testing Patient Information Sheet (Supply T650) in Special Instructions
2. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (Supply T576) is available in Special Instructions.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | NA |
| Lipemia | NA |
| Icterus | NA |
| Other | NA |
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| Whole Blood EDTA | Ambient (preferred) | |
| Refrigerated | ||
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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 one’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 Telangiectasia, ENG and ACVRL1 Full Gene Analysis). Once a mutation has been identified in a family, known mutation analysis can be performed in at-risk family members.
HHT is phenotypically heterogeneous both between families and amongst affected members of the same family. Furthermore, complications associated with HHT have variable ranges of age of onset. Thus, HHT can be diagnostically challenging. Genetic testing for ENG and ACVRL1 mutations allows for the confirmation of a suspected genetic disease. Confirmation of HHT diagnosis will allow for proper treatment and management of the disease, preconception/prenatal counseling, and family counseling. In addition, it has been estimated that genetic screening of suspected HHT individuals and their families is more economically effective than conventional clinical screening.(1)
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
Interpretation Provides information to assist in interpretation of the test results
An interpretive report will be provided.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Absence of a mutation does not preclude the diagnosis of hereditary hemorrhagic telangiectasia (HHT) unless a specific mutation has already been identified in an affected family member. Mutations in ACVRL1 and ENG occur in approximately 80% of individuals with clinically-defined HHT.
Any error in the diagnosis or in the pedigree provided to us, including false-paternity, could lead to erroneous interpretation of results.
Rare, undocumented polymorphisms may be present which could lead to false-negative or false-positive results.
Other targeted mutation analyses available are:
-ENGK/89391 Hereditary Hemorrhagic Telangiectasia, ENG Gene, Known Mutation
-HHTM/89587 Hereditary Hemorrhagic Telangiectasia, ENG and ACVRL1 Large Deletion/Duplication, Molecular Analysis
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Cohen J, Faughnan ME, Letarte M, et al: Cost comparison of genetic and clinical screening in families with hereditary hemorrhagic telangiectasia. Am J of Med Genet A 2005 Aug 30;137(2):153-160
2. Sabba C, Pasculli G, Lenato GM, at al: Hereditary hemorrhagic telangiectasia: clinical features in ENG and ALK1 mutation carriers. J Thromb Haemost. 2007 Jun;5(6):1149-1157
3. Abdalla SA, Letarte M: Hereditary haemorrhagic telangiectasia: current views on genetics and mechanisms of disease.J Med Genet. 2006 Feb;43(2):97-110
4. Guttmacher AE, Marchuk DA, White RI Jr: Hereditary hemorrhagic telangiectasia. N Engl J Med. 1995 Oct 5;333(14):918-924
5. Bayrak-Toydemir P, Mao R, Lewin S, et al: Hereditary hemorrhagic telangiectasia: an overview of diagnosis and management in the molecular era for clinicians. Genet Med 2004;6:175-191
Method Description Describes how the test is performed and provides a method-specific reference
Genomic DNA is extracted from whole blood. The portion of the ACVRL1 gene containing the identified familial mutation is amplified and sequenced in both directions using florescent dye-terminator chemistry. Sequencing products are separated on an automated sequencer and trace files analyzed by mutation detection software and visual inspection for the familial mutation in the exon of interest. (Unpublished Mayo method)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Varies
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
81479 -Unlisted molecular pathology procedure
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
| Result ID | Reporting Name | LOINC Code |
|---|---|---|
| 31053 | ACVRL1 Result | 47961-8 |
| ACVKQ | ACVRL1 Known Mutation Sequencing | In Process |
| 31054 | ACVRL1 Interpretation | 69047-9 |
| 31055 | ACVRL1 Reviewed by | In Process |
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