Berries Health Maturity Onset Diabetes of the Young (MODY) and Diabetes Mellitus (Diabetes) Panel 

This panel investigates genetic variations associated with type 1 and type 2 diabetes mellitus, potential genetic risk factors, and multi-organ complications. Diabetes mellitus (DM) is a metabolic disorder characterized by elevated blood glucose levels (hyperglycemia). Numerous genes have been identified to contribute to the lifetime risk of developing diabetes. 

Genetic factors play a significant role in diabetes predisposition. Monozygotic twins with one affected by T2DM have a 90% chance of the other developing the disease. Approximately 250 genetic variations contribute to the risk of T2DM, affecting various physiological pathways, including insulin synthesis and resistance. 

Purpose of the Diabetes Genetic Test 

The Diabetes genetic testing panel is suitable for individuals with a personal or family history of type 1 or type 2 diabetes, especially if multiple family members are affected or if there are complications associated with diabetes. The test aims to: 

• Confirm diagnoses and guide treatment. 
• Identify at-risk individuals for preventive strategies and management plans. 
• Assist healthcare providers in establishing appropriate diagnoses and facilitating lifestyle modifications. 

Clinical Utility 

The Diabetes genetic testing panel aids in: 

• Establishing accurate diagnoses. 

• Identifying risks for additional symptoms. 

• Personalizing treatment plans. 

• Informing family members of their genetic risk. 

• Connecting patients to relevant resources for support and family planning. 

Methodology 

The test screens for inherited genetic variations (germline mutations) related to type 1 or type 2 diabetes. Genes, composed of DNA sequences, can have different variants impacting health. Important gene mutations related to MODY include variants in the hepatocyte nuclear factor-1-alpha (HNF1A) and glucokinase (GCK) genes. 

The panel evaluates a specified list of genes for genetic changes against human references linked to diabetes conditions. The Berries Health MODY and Diabetes Mellitus Panel is a Laboratory Developed Test (LDT) validated by Berries Health lab partner using Twist Exome 2.0 and Illumina NovaSeq6000 NGS Platform. This test is not FDA-cleared or approved. 

Outcomes of Genetic Test Results 

Positive Result: Indicates a pathogenic variant linked to type 1 or type 2 diabetes. Some cases are dominant (one faulty gene sufficient), while others are recessive (both genes must be faulty). Being a carrier may result in no symptoms but still necessitates management. 

Variant of Uncertain Significance (VUS): Indicates a genetic change not previously associated with diabetes. This may not inform health decisions and could change as more is learned about the variant. 

Negative Result: Indicates no pathogenic variants were found in the tested genes associated with diabetes. 

References and Additional Resources 

1. Genetics Home Reference – MODY: https://ghr.nlm.nih.gov 
2. American Diabetes Association (ADA): https://www.diabetes.org 
3. OMIM (Online Mendelian Inheritance in Man): https://omim.org 
4. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): https://www.niddk.nih.gov 
5. Genetic Testing Registry (GTR): https://www.ncbi.nlm.nih.gov/gtr/ 
6. American College of Medical Genetics and Genomics (ACMG): https://www.acmg.net 
7. Diabetes UK: https://www.diabetes.org.uk 

Limitations of Testing 

This test is designed to identify germline pathogenic variants, including single nucleotide polymorphisms (SNPs) and small insertions and deletions (indels) of up to 1 kilobase pair (kbp). It also analyzes mutations within coding regions and the exon-intron boundaries, specifically within 50 base pairs. Any deletions or duplications larger than 1 kbp that are reportable will be confirmed using orthogonal methods before being included in the final report.

Maturity Onset Diabetes of the Young (MODY) and Diabetes Mellitus (Diabetes) Panel