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| ID | Type | Description | Link |
|---|---|---|---|
| 2U01HG007292-05 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Human Genome Research Institute (NHGRI) | NIH |
| University of Washington | OTHER |
| Seattle Children's Hospital | OTHER |
| University of California, San Francisco |
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The CHARM (Cancer Health Assessment Reaching Many) study will assess the utility of clinical exome sequencing and how it affects care in diverse populations. The study population includes adults at risk for hereditary cancer syndromes.
The primary objective is to implement a hereditary cancer risk assessment program in healthy 18-49 year-olds in primary care settings within a vertically integrated health delivery system (Kaiser Permanente) and a federal qualified health center (Denver Health). The investigators will assess clinical exome sequencing implementation and interpretation, as well as tailored interactions for low health literacy including a contextualized consent process, and a modified approach to results disclosure and genetic counseling. The investigators will also assess the clinical utility (healthcare utilization and adherence to recommended care) and personal utility of primary and additional results from clinical exome sequencing, and evaluate the ethical and policy implications of considering personal utility of genomic information decisions for health care coverage.
Aim 1. Implement a hereditary cancer risk-assessment program in healthy 18-49-year-old adults in primary care settings, with stakeholder input, and offer exome sequencing to clarify risk.
Aim 1A. Identify and recruit 880 adult participants at-risk of a hereditary cancer syndrome.
Aim 1B: Generate medical exome sequence data and interpret variants. Aim 1C: Disclose findings from medical exome sequencing, incorporate results into the electronic medical record (EMR), and facilitate downstream patient management and coordination of care with the provider.
Aim 1D. Engage stakeholders to tailor and optimize the program in diverse populations.
Aim 2. Evaluate and tailor for diverse populations the critical interactions in the program, including the consent process, choices for reporting additional findings, and the response to results disclosure.
Aim 2A. Design, implement, and assess a contextualized consent process to support informed decision-making about participation in research about medical exome sequencing.
Aim 2B. Design, implement, and compare a novel decision aid in the second half of the study for selecting the optional categories of additional findings with the approach we developed in CSER1 that offered a category checklist.
Aim 2C. Design, implement, and compare a modified (communication-focused) approach to results disclosure, genetic counseling, and decision making with a standard (information-focused) approach.
Aim 3. Evaluate the clinical utility (including personal utility) of using exome sequencing to diagnose individuals with hereditary cancer syndromes and provide additional findings.
Aim 3A: Measure the yield of reportable findings for hereditary cancer syndromes and additional findings.
Aim 3B: Evaluate subsequent healthcare utilization for all study participants and adherence to recommended care among individuals who are identified with a hereditary cancer syndrome in diverse settings.
Aim 3C. Assess the personal utility of exome sequencing, including primary and additional findings.
Aim 4. Address pragmatic and ethical challenges to the integration of genomic medicine into clinical and health systems decision-making.
Aim 4A: Develop and pilot a system that integrates genomic, clinical, and healthcare utilization data to inform clinicians and patients acting on genomic information and to reduce care gaps in patient management.
Aim 4B: Advance the analysis of the ethical and policy implications of incorporating personal utility of genomic information into the decision framework for healthcare coverage.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Traditional genetic counseling | Active Comparator | This will be typical genetic counseling that a patient would receive in a traditional genetic counseling setting. |
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| Modified genetic counseling | Experimental | This will be genetic counseling that is modified for a lower literacy patient and will include fewer technical terms and less complicated genetic information. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Modified genetic counseling | Other | After participants at high risk for a hereditary cancer syndrome receive exome sequencing, they will receive modified genetic counseling to help them understand the results. |
| Measure | Description | Time Frame |
|---|---|---|
| Positive Findings for Hereditary Cancer Syndromes | Number of people found to have a pathogenic (P) or likely pathogenic (LP) variant in one of the cancer genes associated with Lynch syndrome or hereditary breast and ovarian cancer | For each person, the test result was available within approximately one month of the receipt of that person's specimen at the laboratory. |
| Measure | Description | Time Frame |
|---|---|---|
| Positive Findings for Other Medically Actionable Genetic Conditions | Number of people with pathogenic variants found in genes related to medically actionable hereditary conditions (other than cancer) | For each person, the test result was available within approximately one month of the receipt of that person's specimen at the laboratory. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michael Leo, PhD | Center for Health Research, Kaiser Permanente Northwest | Principal Investigator |
| Benjamin S Wilfond, MD | Seattle Children's Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Denver Health | Denver | Colorado | 80204 | United States | ||
| Kaiser Permanente Center for Health Research |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37126135 | Derived | Okuyama S, White LL, Anderson KP, Medina E, Deutsch S, Ransom C, Jackson P, Kauffman TL, Mittendorf KF, Leo MC, Bulkley JE, Wilfond BS, Goddard KA, Feigelson HS. Evaluating cancer genetic services in a safety net system: overcoming barriers for a lasting impact beyond the CHARM research project. J Community Genet. 2023 Jun;14(3):329-336. doi: 10.1007/s12687-023-00647-x. Epub 2023 May 1. | |
| 35689290 | Derived | Mittendorf KF, Lewis HS, Duenas DM, Eubanks DJ, Gilmore MJ, Goddard KAB, Joseph G, Kauffman TL, Kraft SA, Lindberg NM, Reyes AA, Shuster E, Syngal S, Ukaegbu C, Zepp JM, Wilfond BS, Porter KM. Literacy-adapted, electronic family history assessment for genetics referral in primary care: patient user insights from qualitative interviews. Hered Cancer Clin Pract. 2022 Jun 10;20(1):22. doi: 10.1186/s13053-022-00231-3. |
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Genotype and Phenotype data will be uploaded to ANVIL. Variant data will be uploaded to ClinVar.
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Data will be loaded to ANVIL and ClinVar at least annually beginning in 2018.
Subject to ANVIL and ClinVar regulations.
967 people were eligible and consented. Of those, 827 submitted a sample for testing. 131 of those people were lost to follow up, declined to receive results, or received a mailed letter with their results. Every outcome measure defined a different analytic sample. Randomization was implemented for only one of the study aims and only applies to outcome measures 6 and 7. Randomization occurred after test results were available.
Recruitment took place between August 2018 and August 2020 through email, text, and post-cards. Interested patients between 18 and 49 years completed a web-based family history risk assessment to determine eligibility. Participants who screened as high risk were provided with the options to receive exome based panel testing through the study. Participants who consented were provided a saliva sample collection kit that could be returned by mail or to their clinic.
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| ID | Title | Description |
|---|---|---|
| FG000 | People Were Eligible and Consented | All individuals eligible and consent for the study |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||||||||||||||
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| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Baseline Participants | All participants who were eligible and consented |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Positive Findings for Hereditary Cancer Syndromes | Number of people found to have a pathogenic (P) or likely pathogenic (LP) variant in one of the cancer genes associated with Lynch syndrome or hereditary breast and ovarian cancer | CHARM participants who were sent a saliva collection kit, returned their sample to the laboratory, had successful DNA extraction, and sequencing was completed. There was no randomization, and therefore no separate "arms" for this analysis. | Posted | Count of Participants | Participants | For each person, the test result was available within approximately one month of the receipt of that person's specimen at the laboratory. |
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N/a. Adverse event data was not collected for this study. This data would not result from the CHARM study procedures. The IRB did not require adverse event data collection.
No study-related adverse events would reasonably be expected to result from the CHARM study procedures. The IRB did not require adverse event data collection.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | All Enrolled Participants | Participants who enrolled in the CHARM study who were sent a saliva collection kit. There was no randomization, and therefore no separate "arms" for this analysis. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Joanna Bulkley, PhD | Kaiser Permanente Center for Health Research | 5033352400 | joanna.e.bulkley@kpchr.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 11, 2019 | Dec 4, 2019 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Oct 24, 2019 | Dec 4, 2019 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D009386 | Neoplastic Syndromes, Hereditary |
| D003123 | Colorectal Neoplasms, Hereditary Nonpolyposis |
| D061325 | Hereditary Breast and Ovarian Cancer Syndrome |
| ID | Term |
|---|---|
| D009369 | Neoplasms |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D015179 | Colorectal Neoplasms |
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| OTHER |
| Denver Health and Hospital Authority | OTHER |
| Emory University | OTHER |
| Dana-Farber Cancer Institute | OTHER |
| Columbia University | OTHER |
All participants will receive exome sequencing. The randomization will be into one of two types of genetic counseling - traditional and modified.
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The participant will not know if they are receiving traditional or modified genetic counseling.
| Traditional genetic counseling | Other | After participants at high risk for a hereditary cancer syndrome receive exome sequencing, they will receive traditional genetic counseling to help them understand the results. |
|
| Positive Findings for a Selected List of Carrier Conditions |
Number of people with pathogenic variants found in genes related to common carrier conditions |
| For each person, the test result was available within approximately one month of the receipt of that person's specimen at the laboratory. |
| Number of Participants With Healthcare Utilization Measured Via Electronic Medical Record (EMR) Data | Downstream healthcare utilization of specific recommended procedures (e.g., colonoscopy, mammography, surgery) will be compared between CHARM participants who received at least one actionable risk management recommendation from study genetic counselors and those who did not receive an actionable risk management recommendation. | Within 12 months of participant receiving information about their hereditary cancer syndrome risk |
| Participant Understanding of Recommended Care | Measurement of participant's understanding of the recommended care based on their genetic test result will be assessed using a validated survey tool | 2 weeks post result disclosure, 6 months post result disclosure |
| Participant Understanding of Genetic Test Results | "Perceived understanding of results" This novel 5-item measure asked, "Thinking about only your cancer genetic test result, please rate how strongly you agree or disagree with each of the following statements." The 5 items were assessed on a 5-point Likert scale (1 = strongly disagree to 5 = strongly agree). A principal-axis factor analysis strongly supported a 1 factor solution (accounting for 65.4% of the variance in these items), providing evidence for structural validity, and a Cronbach's α of 0.90, providing strong evidence for internal consistency. The scale was scored using the mean; thus, the possible scores can range from 1 to 5, with higher scores indicating greater understanding. | 2 weeks post genetic result disclosure |
| Participant Satisfaction of Genetic Counseling | This novel measure consisted of 4 items adapted from the Patient Assessment of Communication Effectiveness scale, 8 items developed by the consortium related to participants' overall satisfaction with the results and experience of results disclosures, and 6 items that focused on key elements of modified genetic counseling. Items were measured on a 5-point Likert scale (1 = strongly disagree to 5 = strongly agree). Using principal-axis factor analyses using oblique rotation, we found the 3-factor solution (accounting for 62.5% of the variance in the items) to provide adequate simple structure with conceptually meaningful factors and thus, created subscale scores for each set of items (6 loaded on each factor): "genetic counseling relationship score", "communication difficulty score", and "communication ease score". The possible mean scores can range from 1 to 5, with higher scores indicating a better outcome. | 2 weeks post genetic results disclosure |
| Family Communication | Measurement of the degree to which participants shared their genetic test results with various family members will be assessed using a validated survey tool | Assessed 6 months post result disclosure |
| Personal Utility of Genomic Sequencing (Qualitative Interview Only) | Participant's perceived utility of obtaining genetic testing and genetic counseling were assessed. Data collection used semi-structured qualitative interviews. Analyses were conducted using a modified grounded theory approach and explored the five utility domains of the model: clinical, emotional, behavioral, cognitive, and social. The analysis examined how well this multifaceted perceived utility model applied to the responses provided during the interviews. The qualitative data was not quantified in any way and can not be represented in a tabular format. | Qualitative interviews were conducted within 1 month of results disclosure; a subset of these participants were interviewed again at 6 months post-results disclosure. |
| Portland |
| Oregon |
| 97227 |
| United States |
| 33984519 | Derived | Mittendorf KF, Kauffman TL, Amendola LM, Anderson KP, Biesecker BB, Dorschner MO, Duenas DM, Eubanks DJ, Feigelson HS, Gilmore MJ, Hunter JE, Joseph G, Kraft SA, Lee SSJ, Leo MC, Liles EG, Lindberg NM, Muessig KR, Okuyama S, Porter KM, Riddle LS, Rolf BA, Rope AF, Zepp JM, Jarvik GP, Wilfond BS, Goddard KAB; CHARM study team. Cancer Health Assessments Reaching Many (CHARM): A clinical trial assessing a multimodal cancer genetics services delivery program and its impact on diverse populations. Contemp Clin Trials. 2021 Jul;106:106432. doi: 10.1016/j.cct.2021.106432. Epub 2021 May 11. |
| Received negative results by mailed letter |
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| Lost to Follow-up |
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| years |
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| Sex: Female, Male | Sex assigned at birth | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Household income | Count of Participants | Participants |
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| Education level | Count of Participants | Participants |
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| Secondary | Positive Findings for Other Medically Actionable Genetic Conditions | Number of people with pathogenic variants found in genes related to medically actionable hereditary conditions (other than cancer) | 827 is the number of CHARM participants who were sent a saliva collection kit, returned their sample to the laboratory, had successful DNA extraction, and sequencing was completed. There was no randomization, and therefore no separate "arms" for this analysis. | Posted | Count of Participants | Participants | For each person, the test result was available within approximately one month of the receipt of that person's specimen at the laboratory. |
|
|
|
| Secondary | Positive Findings for a Selected List of Carrier Conditions | Number of people with pathogenic variants found in genes related to common carrier conditions | 810 is the number of CHARM participants who were sent a saliva collection kit, returned their sample to the laboratory, had successful DNA extraction, affirmatively chose to receive "additional findings", and sequencing was completed. Samples from participants who did not choose additional findings were not tested for carrier conditions. There was no randomization, and therefore no separate "arms" for this analysis. . | Posted | Count of Participants | Participants | For each person, the test result was available within approximately one month of the receipt of that person's specimen at the laboratory. |
|
|
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| Secondary | Number of Participants With Healthcare Utilization Measured Via Electronic Medical Record (EMR) Data | Downstream healthcare utilization of specific recommended procedures (e.g., colonoscopy, mammography, surgery) will be compared between CHARM participants who received at least one actionable risk management recommendation from study genetic counselors and those who did not receive an actionable risk management recommendation. | For this analysis participants were not pre-specified to be separated by type of genetic counseling administered. The analysis sample excluded participants: 1) inadequate exome sequencing sample; 2) died or disenrolled before result disclosure; 3) for each procedure (e.g. mammography, colonoscopy, risk-reducing mastectomy ) individuals without relevant organ(s) at study entry. 4) Except for colonoscopy, those who did not reported their sex at birth as female. | Posted | Count of Participants | Participants | Within 12 months of participant receiving information about their hereditary cancer syndrome risk |
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| Secondary | Participant Understanding of Recommended Care | Measurement of participant's understanding of the recommended care based on their genetic test result will be assessed using a validated survey tool | The study determined that collecting the data on this secondary outcome was not feasible and did not include these questions on surveys or interviews. We did not analyze this outcome. | Posted | 2 weeks post result disclosure, 6 months post result disclosure |
|
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| Secondary | Participant Understanding of Genetic Test Results | "Perceived understanding of results" This novel 5-item measure asked, "Thinking about only your cancer genetic test result, please rate how strongly you agree or disagree with each of the following statements." The 5 items were assessed on a 5-point Likert scale (1 = strongly disagree to 5 = strongly agree). A principal-axis factor analysis strongly supported a 1 factor solution (accounting for 65.4% of the variance in these items), providing evidence for structural validity, and a Cronbach's α of 0.90, providing strong evidence for internal consistency. The scale was scored using the mean; thus, the possible scores can range from 1 to 5, with higher scores indicating greater understanding. | Of the 827 patients with samples sequenced, 352 received results using modified genetic counseling and 344 received results using traditional genetic counseling. A total of 65 patients received their negative results by mailed letter, 3 declined to receive results, and 63 were lost to follow up. Of the 696 patients randomized, 582 completed the post-results survey. Of these 582, 571 provided the responses required for inclusion in this analysis. | Posted | Mean | 95% Confidence Interval | score on a scale | 2 weeks post genetic result disclosure |
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| Secondary | Participant Satisfaction of Genetic Counseling | This novel measure consisted of 4 items adapted from the Patient Assessment of Communication Effectiveness scale, 8 items developed by the consortium related to participants' overall satisfaction with the results and experience of results disclosures, and 6 items that focused on key elements of modified genetic counseling. Items were measured on a 5-point Likert scale (1 = strongly disagree to 5 = strongly agree). Using principal-axis factor analyses using oblique rotation, we found the 3-factor solution (accounting for 62.5% of the variance in the items) to provide adequate simple structure with conceptually meaningful factors and thus, created subscale scores for each set of items (6 loaded on each factor): "genetic counseling relationship score", "communication difficulty score", and "communication ease score". The possible mean scores can range from 1 to 5, with higher scores indicating a better outcome. | The number analyzed in each row differs from overall number analyzed because some participants did not respond to all questions in the survey resulting in missing data. For each analysis we used all available data. | Posted | Mean | 95% Confidence Interval | score on a scale | 2 weeks post genetic results disclosure |
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| Secondary | Family Communication | Measurement of the degree to which participants shared their genetic test results with various family members will be assessed using a validated survey tool | For this analysis, participants were not pre-specified to be separated by type of genetic counseling administered. Survey data from 562 CHARM participants who received genetic test results and completed survey questions on family communication were available for analysis. | Posted | Count of Participants | Participants | Assessed 6 months post result disclosure |
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| Secondary | Personal Utility of Genomic Sequencing (Qualitative Interview Only) | Participant's perceived utility of obtaining genetic testing and genetic counseling were assessed. Data collection used semi-structured qualitative interviews. Analyses were conducted using a modified grounded theory approach and explored the five utility domains of the model: clinical, emotional, behavioral, cognitive, and social. The analysis examined how well this multifaceted perceived utility model applied to the responses provided during the interviews. The qualitative data was not quantified in any way and can not be represented in a tabular format. | Not Posted | Qualitative interviews were conducted within 1 month of results disclosure; a subset of these participants were interviewed again at 6 months post-results disclosure. | Participants |
| 0 |
| 0 |
| 0 |
| 0 |
| 0 |
| 0 |
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| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D049914 | DNA Repair-Deficiency Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D001943 | Breast Neoplasms |
| D010051 | Ovarian Neoplasms |
| D004701 | Endocrine Gland Neoplasms |
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D000091662 | Genital Diseases |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
| Communication difficulty score |
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| Genetic counseling relationship score |
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