genetic testing

Test indications include suspected genetic disorders in children and adults for whom a targeted genetic testing approach is likely to be low yield or has already failed.

Analytic validity, diagnostic yield and clinical utility are similar or superior to other clinical genetic tests, such as exome sequencing, chromosomal microarray analysis and next-generation sequencing gene panel tests.

Appropriate adoption of genome sequencing as a molecular diagnostic test in Canada would be facilitated by a cohesive national strategy for genomic medicine.

Genetic testing of patient constitutional DNA (i.e., their genome) is increasingly performed in medical practice. 1–3 Sequencing an entire human genome (about 3.2 billion nucleotides) is now possible to complete in days to weeks, and at a similar cost to some advanced imaging tests or to a brief admission to hospital.3,4 Genome sequencing is being integrated into health care systems internationally, most notably in the United Kingdom.5 Starting in 2021, genome sequencing is being performed as a clinical genetic test in Ontario, Canada.

Author/s:

Costain, G., Cohn, R. D., Scherer, S. W., Marshall, C. R.

APOE ɛ4 Allele Testing and Risk of Alzheimer Disease

Carly Hughes — Sat, 16 Jan 2021 19:31:55 +0000

Date Added:

January 16, 2021

Journal/Publication:

Journal of the American Medical Association

Publisher:

Journal of the American Medical Association

Publication Date:

January 14, 2021

URL:

APOE ɛ4 Allele Testing and Risk of Alzheimer Disease

Type:

Clinical Decision Aids

Format:

Article

DOI (1):

doi:10.1001/jama.2020.15085

Keywords

MeSH

A brief review of the interpretation of APOE tests for diagnosing and predicting dementia of the Alzheimer’s type. James W. Mold, MD, MPH

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A 64-year-old man presented with concern about an abnormal genetic test result for apolipoprotein E (APOE) obtained through his primary care physician. He reported forgetfulness and word-finding difficulties for 3 years but performed all activities of daily living independently and was generally healthy. His father and maternal great aunt developed dementia in their 70s. Physical (including neurologic) examination, basic laboratory studies, and brain magnetic resonance imaging results were normal. The Short Test of Mental Status (STMS) score was 33 (maximal attainable score of 38 indicates best performance). Neuropsychological assessment showed average to above-average performance in all cognitive domains, accounting for age and education. Results of his genetic testing for APOE were reported as follows: “This individual possesses an apolipoprotein E genotype (3 and 4) that indicates, with high specificity, that Alzheimer’s disease is the cause of or a contributor to the observed dementia.

Author/s:

Choudhury, Parichita, Boeve, Bradley F., Ramanan, Vijay K

Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer: US Preventive Services Task Force Recommendation Statement.

Brian Desmarais — Wed, 21 Aug 2019 19:42:45 +0000

Date Added:

August 21, 2019

Journal/Publication:

Journal of the American Medical Association

Publication Date:

August 20, 2019

URL:

Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer: US Preventive Services Task Force Recommendation Statement.

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2019.10987

Keywords

MeSH

early detection of cancer

Genetic Counseling

I suspect you are already doing this, but since it is making a splash on the TV news programs, I thought you ought to see it. James W. Mold, MD, MPH

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IMPORTANCE:

Potentially harmful mutations of the breast cancer susceptibility 1 and 2 genes (BRCA1/2) are associated with increased riskfor breast, ovarian, fallopian tube, and peritoneal cancer. For women in the United States, breast cancer is the most common cancer after nonmelanoma skin cancer and the second leading cause of cancer death. In the general population, BRCA1/2 mutations occur in an estimated 1 in 300 to 500 women and account for 5% to 10% of breast cancer cases and 15% of ovarian cancer cases.

OBJECTIVE:

To update the 2013 US Preventive Services Task Force (USPSTF) recommendation on risk assessment, genetic counseling, and genetic testing for BRCA-related cancer.

EVIDENCE REVIEW:

The USPSTF reviewed the evidence on risk assessment, genetic counseling, and genetic testing for potentially harmful BRCA1/2 mutations in asymptomatic women who have never been diagnosed with BRCA-related cancer, as well as those with a previous diagnosis of breast, ovarian, tubal, or peritoneal cancer who have completed treatment and are considered cancer free. In addition, the USPSTF reviewed interventions to reduce the risk for breast, ovarian, tubal, or peritoneal cancer in women with potentially harmful BRCA1/2 mutations, including intensive cancer screening, medications, and risk-reducing surgery.

FINDINGS:

For women whose family or personal history is associated with an increased risk for harmful mutations in the BRCA1/2 genes, or who have an ancestry associated with BRCA1/2 gene mutations, there is adequate evidence that the benefits of risk assessment, genetic counseling, genetic testing, and interventions are moderate. For women whose personal or family history or ancestry is not associated with an increased risk for harmful mutations in the BRCA1/2 genes, there is adequate evidence that the benefits of risk assessment, genetic counseling, genetic testing, and interventions are small to none. Regardless of family or personal history, the USPSTF found adequate evidence that the overall harms of risk assessment, genetic counseling, genetic testing, and interventions are small to moderate.

CONCLUSIONS AND RECOMMENDATION:

The USPSTF recommends that primary care clinicians assess women with a personal or family history of breast, ovarian, tubal, or peritoneal cancer or who have an ancestry associated with BRCA1/2 gene mutations with an appropriate brief familial risk assessment tool. Women with a positive result on the risk assessment tool should receive genetic counseling and, if indicated after counseling, genetic testing. (B recommendation) The USPSTF recommends against routine risk assessment, genetic counseling, or genetic testing for women whose personal or family history or ancestry is not associated with potentially harmful BRCA1/2 gene mutations. (D recommendation).

Author/s:

US Preventive Services Task Force

Consistency of Direct to Consumer Genetic Testing Results Among Identical Twins

Brian Desmarais — Wed, 19 Jun 2019 00:34:45 +0000

Date Added:

June 18, 2019

Journal/Publication:

The American Journal of Medicine

Publication Date:

June 15, 2019

URL:

Consistency of Direct to Consumer Genetic Testing Results Among Identical Twins

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1016/j.amjmed.2019.04.052

Keywords

MeSH

Direct-To-Consumer Screening and Testing

This study calls into question the accuracy of direct-to-consumer genetic testing. James W. Mold, MD, MPH

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Abstract

Purpose

To evaluate the consistency of 3 commonly used direct to consumer genetic testing kits.

Background

Genetic testing kits are widely marketed by several companies but the consistency of their results is unclear. Since identical twins share the same DNA, their genetic testing results should provide insight into test consistency.

Methods

42 identical twins (21 pairs) provided samples for three testing companies. Outcomes were concordance of ancestry results when i) twin pairs were tested by the same company and ii) the same participant was tested by different companies. Concordance of 8 self-reported traits with 23andMe genetic analyses were also examined.

Results

Concordance of ancestry results when twin pairs were tested by the same company was high, with mean percent agreement ranging from 94.5%–99.2%. Concordance of ancestry results when participants were tested by two different companies was lower, with mean percent agreement ranging from 52.7%–84.1%. Concordance of trait results was variable, ranging from 34.1% for deep sleep and detached earlobes to 90.2% for cleft chin.

Conclusion

The consistency of consumer genetic testing is high for ancestry results within companies but lower and more variable for ancestry results across companies and for specific traits. These results raise questions about the usefulness of such testing.

Author/s:

Huml, A.M., Sullivan C., Figueroa, M., Scott, K., Sehgal, A.R.