ENDURE Study

Studying individuals with a monogenic beta cell disorder caused by a distinct pathogenic single genetic variant will allow us to study and define the direct effects of the genetic variant on cellular and molecular function, specifically how this affects beta cell development, function, and destruction. A clear description of effects may enable us to refine our understanding of beta cell development and function and may allow us to improve disease management.

Monogenic beta cell disorders are rare, where a single alteration in a pathway leads to disease. They can therefore be described as extreme cases of polygenic beta cell disorders where multiple pathways are slightly dysfunctional and these multifactorial alterations lead to disease. Study of the monogenic disorder will provide unprecedented insight into how more common beta cell disorders develop, particularly regarding how the immune system interacts with beta cells.

The ENDURE study aims to improve our understanding of the molecular and physiological mechanisms that underlie beta cell disorders by studying individuals with a pathogenic genetic variant.

Objectives

• To identify and describe biomarkers and cellular features in blood samples that occur because of the rare causal genetic variant.
• To study the altered physiology or cellular function that are due to the rare causal genetic variant.

Outcomes

• Identification and description of biomarkers or cellular features associated with specific rare causal genetic variants.
• Identification of alterations in physiological function with specific rare genetic variants.

 Inclusion Criteria

Core Study: Blood collection – 6 years of age and olderImaging Sub-Study: MRI scan: 6 years of age and olderParticipants will have:

• Adult: mental capacity to give informed consent
• Child: parent/guardian has mental capacity to give informed consent, and child has capacity to give assent (which will be provided in an age-adjusted format).
• any sex, ethnicity, location.

Eligibility to have a different procedure is age dependent, as outlined below.

Specific inclusion criteria

Group 1: Cases:

• Known to have a genetic variant(s) resulting in a beta cell disorder.

Group 2: Controls:

• Not known to have a genetic variant(s) resulting in a beta cell disorder.
• Matched for age (+/- 15%)
• Matched for BMI (+/- 3 kg/m²).

Exclusion Criteria

Exclusions for Core Procedure:

• Blood collection – age <6 years or age >99 years
• Adult: lacks mental capacity to give informed consent
• Child: parent/guardian lacks mental capacity to give informed consent

Exclusions for MRI assessments:

Age <6 years or age >99 years

Cochlear Implant; Aneurysm Clips; Neurological stimulator; Implanted cardiac devices (ICD, PPM, loop recorders, or any others); Metal heart valve; History of metal foreign bodies in orbits; Other implanted metal device which prevents MRI

Known claustrophobia.