Author: Zhang Li
Unit: Department of Clinical Laboratory, Zhongshan Hospital, Fudan University
Single-gene genetic diseases usually refer to genetic diseases controlled by a pair of pairs/one alleles, common red-green blindness, hemophilia, albinism, etc., which have posed a greater threat to human health. At present, the rapid development of high-throughput sequencing technology has also made genetic testing widely used in the auxiliary diagnosis of such diseases.
However, in actual clinical work, because different clinicians have different understandings of the variations in the report, the results of the interpretation of the test report will also vary from person to person. According to domestic and foreign guidelines or consensus, this paper briefly describes how to interpret the genetic test report of single-gene genetic diseases.
Essential elements of a genetic test report for a single genetic disease
On December 26, 2018, China's first "Specification for Genetic Testing Reports for Clinical Single-Gene Genetic Diseases" (standard number T/SZGIA 4-2018) was officially released. This standard specifies the content and requirements that should be included in the genetic test report for clinical single-gene genetic diseases:
1. Detect basic information
The information and contact information of the testing institution, the basic information of the subject, the information of the institution and the physician, the type of test sample, the date of sample receipt and test report, the test items and test methods.
2. Test results
Information about the site of variation, naming of sites of variation, selection of transcripts, determination of pathogenicity of sites of variations, and grading reports of sites of variations.
3. Test conclusion
The U.S. Standards and Specifications for Clinical Genetics Test Reporting emphasize that only relevant causative/suspected causative variants should be reported if minor and accidental findings need to be reported; for variants that are clinically interpreted as benign and suspected benign, it is not necessary to report; and for variants of unknown clinical significance, it is recommended to report variants related to the subject's indication only if the conclusion is undecided.
4. Explanation of results
List specific evidence to assess the pathogenicity of detected variants, cite referenced databases and literature, assess the relevance of variants to phenotypes, and explain genetic patterns and genetic risks.
5. Suggestions
Subjects are advised to receive genetic counseling based on the results of the test report, and if variants associated with the subject's clinical phenotype are detected, a lineage analysis is recommended.
6, References
Lists the references cited in the report.
7. Description and limitations of detection methods
The test method should be briefly described, including the material to be tested and the testing steps, and the scope and limitations of the corresponding method should be explained. Indicate clinically validated technical parameters, including sensitivity and specificity for various types of variant detection.
8. Signature and signature
Including the author of the inspection report, the checker of the report results, and the final reviewer and issuer of the report. You can use a physical signature or an electronic signature.
Considerations for the interpretation of gene test reports for single-gene genetic diseases
In the single-gene genetic disease genetic test report, the interpretation difficulties are mainly concentrated in the test conclusion part. According to the relevant guidelines of the American Society of Medical Genetics and Genomics (ACMG), the "Clinical Genetic Testing Report Specification and Genetic Testing Industry Consensus Discussion" and the "American Clinical Genetics Test Report Standards and Specifications", the main points of interpretation of the content involved in this part are as follows:
With the improvement of people's health awareness and the increase of screening awareness, single-gene genetic testing for genetic diseases has become more and more popular. As a report interpreter, you should constantly update your knowledge reserves in this area for a more scientific and accurate interpretation. It is necessary not to cause unnecessary mental burden to patients, but also to explain the clinical significance of test results as clearly as possible, and to be responsible for patients and their families.
Edited by: Yeah Reviewer: Xiao Ran