BMPR1A Gene, Full Gene Analysis
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Juvenile polyposis syndrome (JPS) is a rare hereditary cancer predisposition syndrome caused by mutations in the SMAD4 or BMPR1A genes. JPS is characterized by the presence of multiple histologically defined juvenile polyps in the upper and/or lower gastrointestinal (GI) tract and an increased risk for GI cancers. Age of onset for cancer development is typically in the second or third decade of life, although some patients present with a more severe infantile-onset form of the disease. JPS is inherited in an autosomal dominant fashion, although a significant proportion of probands have no family history. Approximately 50% of patients with JPS have an identifiable mutation in the SMAD4 or BMPR1A genes.
Confirmation of juvenile polyposis syndrome for patients with clinical features
This test should be ordered only for individuals with symptoms suggestive of juvenile polyposis syndrome. Asymptomatic patients with a family history of juvenile polyposis syndrome should not be tested until a mutation has been identified in an affected family member.
All detected alterations are evaluated according to American College of Medical Genetics recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Some individuals who are carriers or have a diagnosis of juvenile polyposis syndrome may have a mutation that is not identified by this method (eg, promoter mutations). The absence of a mutation, therefore, does not eliminate the possibility of positive carrier status or the diagnosis of juvenile polyposis syndrome. For carrier testing, it is important to first document the presence of a BMPR1A gene mutation in an affected family member.
We strongly recommend that patients undergoing predictive testing receive genetic counseling both prior to testing and after results are available.
In some cases, DNA alterations of undetermined significance may be identified.
Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.
A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories at 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.
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.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for standards for interpretation and reporting of sequence variations: Revisions 2007. Genet Med 2008 Apr;10(4):294-300
2. Lammi L, Arte S, Somer M, et al: Mutations in AXIN2 cause familial tooth agenesis and predispose to colorectal cancer. Am J Hum Genet 2004;74:1043-1050
3. Liu W, Dong X, Mai M, et al: Mutations in AXIN2 cause colorectal cancer with defective mismatch repair by activating beta-catenin/TCF signaling. Nat Genet 2000;26:146-147
4. Mai M, Qian C, Yokomizo A, et al: Cloning of the human homolog of conductin (AXIN2), a gene mapping to chromosome 17q23-q24. Genomics 1998;55:341-344
5. Dong X, Seelan RS, Qian C, et al: Genomic structure, chromosome mapping and expression analysis of the human AXIN2 gene. Cytogenet Cell Genet 2001;93:26-28