Genetic Analysis of Uncommon Disease Presentations in Non-US Populations

Study Description:

We plan to couple novel techniques of genomic interrogation with more traditional methods involved in genetic discovery to investigate a broad range of diseases and conditions in locations without access to medical genetics for which there exists strong evidence that genetic factors are contributory.

Objectives:

Primary Objective: To investigate the genetic contribution to conditions displaying unconventional clinical phenotypes/familial segregation among individuals belonging to historically underrepresented populations.

Secondary Objective: To develop an international collaborative network across countries with limited or no access to medical genetics.

Tertiary/Exploratory Objective: To identify the psychosocial impact and cultural considerations of the diagnostic odyssey in countries without medical genetics access to better inform genetic counseling practices for these populations.

Endpoints:

Primary Endpoint: Exhaustion of available genomic interrogation techniques to determine the etiology of unconventional clinical phenotypes.

Secondary Endpoint: Independence and autonomy when conducting genetic studies among sites with limited to no access to medical genetics.

Tertiary/Exploratory Endpoint: Elucidation of psychosocial impact and cultural considerations for patients with limited access to medical genetics.

• INCLUSION CRITERIA:

To be eligible to participate in this study, an individual must meet all of the following criteria:

• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Probands aged >2 years at enrollment or first-degree relatives of probands (age >2 years).
• Suspicion of genetic etiology of illness due to strong family history, precocious onset, severity or mildness of phenotype, or all factors being present.
• Affected individuals and unaffected family members, determination of clinical criteria for inclusion will be determined by medical record review prior to participation.
• Ability of participant and their parent or guardian to understand and have willingness to sign a written informed consent and/or assent document.

Exclusion criteria

An individual who meets any of the following criteria will be excluded from participation in this study:

• Anyone unwilling to provide informed consent (for themselves as adults, on behalf of their children as minors, or on behalf of an adult who is unable to provide consent for themselves) or assent.
• Individuals who have undergone diagnostic testing for a genetic condition AND the test results were positive.
• Evidence that symptoms are secondary or caused by an undiagnosed condition that is unlikely to have a genetic cause.
• In the opinion of the investigator, participant has a condition that would preclude participation in the study by interfering with the participant s ability to engage in the required protocol evaluation and testing.