Test ID: BMPRZ    
BMPR1A Gene, Full Gene Analysis, Varies

Confirmation of juvenile polyposis syndrome for patients with clinical features

When this test is ordered, comparative genomic hybridization array will always be performed at an additional charge.

See Colonic Polyposis Syndromes Testing Algorithm in Special Instructions.

Juvenile polyposis syndrome (JPS) is a rare hereditary cancer predisposition syndrome caused by alterations 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 alteration in the SMAD4 or BMPR1A genes.

An interpretive report will be provided.

All detected alterations are evaluated according to American College of Medical Genetics and Genomics (ACMG) recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Some individuals who are carriers or have a diagnosis of juvenile polyposis syndrome may have a variant that is not identified by this method (eg, promoter alterations). The absence of a variant, 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 alteration in an affected family member.

It is strongly recommended 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 alterations 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.

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.

1. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May;17(5):405-424

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

• Molecular Genetics: Inherited Cancer Syndromes Patient Information
• Informed Consent for Genetic Testing
• Colonic Polyposis Syndromes Testing Algorithm
• Informed Consent for Genetic Testing (Spanish)