STK11 Gene, Known Mutation
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Peutz-Jeghers syndrome (PJS) is an autosomal dominant disorder characterized by gastrointestinal (GI) hamartomatous polyps and melanotic macules. The GI polyps are most common in the small intestine. Although typically benign, these polyps can cause chronic bleeding and may result in obstruction and intussusception. Pigment changes, typically dark blue spots around the lips, buccal mucosa, and fingers, appear in childhood. Affected individuals are also at an increased risk for a variety of malignancies including colorectal, gastric, breast, thyroid, pancreatic, uterine, and sertoli cell and sex cord tumors. PJS is caused by mutations in the STK11 (formerly LKB1) gene.
Note: This test is appropriate for predictive testing in families in which a point mutation or small insertion/deletion/duplication has been identified.
SDEL / Single-Gene Large Deletion and Duplication Analysis is appropriate for predictive testing in families in which a large deletion or duplication (whole exon or multi-exon) has been identified.
If a familial mutation has not been previously identified, full analysis of the STK11 gene is more appropriate (see STKMS / STK11 Gene, Full Gene Analysis).
Confirming a diagnosis of Peutz-Jeghers syndrome
Screening at-risk individuals when a point mutation or small insertion/deletion/duplication in the STK11 gene has been identified in an affected family member
All detected alterations will be evaluated according to American College of Medical Genetics and Genomics (ACMG) recommendations.(1) Variants will be 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
The identification of a disease-causing mutation in an affected family member is necessary before predictive testing for other family members can be offered. If a familial mutation has not been previously identified, order STKMS / STK11 Gene, Full Gene Analysis.
Analysis is performed for the familial mutation provided only. This assay does not rule out the presence of other mutations within this gene or within other genes that may be associated with Peutz-Jeghers syndrome.
We strongly recommend that patients undergoing predictive testing receive genetic counseling both prior to testing and after results are available.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Any error in the diagnosis or in the pedigree provided to us, including false-paternity, could lead to erroneous interpretation of results.
A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.
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 of interpretation and reporting of sequence variations: revisions 2007. Genet Med 2008:10(4):294-300
2. Amos CI, Frazier ML, Wei C, McGarrity TJ: Peutz-Jeghers Syndrome. In GeneReviews [Internet]. Edited by RA Pagon, TD Bird, CR Dolan, et al. University of Washington, Seattle, Updated 2011 Feb 22
3. Beggs AD, Latchford AR, Vasen HF, et al: Peutz-Jeghers syndrome: a systematic review and recommendations for management. Gut 2010 Jul;59(7):975-986
4. Hearle N, Schumacher V, Menko FH, et al: Frequency and spectrum of cancers in the Peutz-Jeghers syndrome. Clin Cancer Res 2006 May 15;12(10):3209-3215