Maturity Onset Diabetes of the Young (MODY), and Diabetes Mellitus (Diabetes) Panel:
This panel investigates genetic variances related to type I or II diabetes mellitus disorders, potential genetic risk factors as well as multi organ complications. Diabetes mellitus (DM) is a metabolic disease, involving inappropriately elevated blood glucose levels (hyperglycemia). Multiple genes are reported to directly or indirectly contribute to the life-time risk of developing diabetes mellitus.
What are type I or II diabetes mellitus disorders:
Diabetes mellitus disorders are medically defined as disorders of inadequate control of blood levels of glucose that affect multiple systems through the body. Diabetes mellitus (DM) has many subclassifications, including type 1, type 2, maturity-onset diabetes of the young (MODY), gestational diabetes, neonatal diabetes, and steroid-induced diabetes. The main subtypes of DM are Type 1 diabetes mellitus (T1DM) and Type 2 diabetes mellitus (T2DM), which classically result from defective insulin secretion (T1DM) and/or action (T2DM). T1DM presents in children or adolescents, while T2DM is thought to affect middle-aged and older adults who have prolonged hyperglycemia due to poor lifestyle and dietary choices. The pathogenesis for T1DM and T2DM is drastically different, and therefore each type has various etiologies, presentations, and treatments.
In many cases, type I or II diabetes mellitus diseases run in families and there is a genetic root for these disorders. Monozygotic twins with one affected twin have a 90{788689b1f96e6e5a29b7ebdc0a74f574bcea9748ac8e484e1c92285099e82813} likelihood of the other twin developing T2DM in his/her lifetime. Several genes are known to cause type I, neonatal or congenital diabetes. Approximately 250 genetic variations to date have been described to contribute to the risk for T2DM. These genes encode for proteins involved in various pathways leading to DM, including pancreatic development, insulin synthesis, secretion, and development, amyloid deposition in beta cells, insulin resistance, and impaired gluconeogenesis regulation. The Diabetes next generation sequencing (NGS) panel investigate germline variations in genes associated with these disorders, and other hyperglycemia conditions that may present with similar phenotypes.
What is the outcome of genetic test results:
A. Positive Result.
A positive test result indicates a pathogenic variant linked to type I or II diabetes mellitus disorder has been identified. In some cases, type I or II diabetes mellitus disorders are dominant in which one copy of defective gene is sufficient to cause the disease. Some other type I or II diabetes mellitus disorders are recessive disorders, meaning that both copies of defective genes must be present to cause the disease. Having a heterozygous pathogenic variation means that the individual is a carrier of the disease and may not experience the disease condition. This knowledge provides the patient and health care provider an opportunity to understand and, in some cases, manage their treatment plans.
B. Variation of uncertain significance (VUS).
If genetic testing shows a change that has not been previously associated with type I or II diabetes mellitus disorders, the person’s test result may report a VUS. This result may be interpreted as uncertain, which is to say that the information does not help to clarify contribution of VUS to disease condition and is typically not considered in making health care decisions. Some gene variants may be reclassified as researchers learn more about variants. Variants that initially classified as variants of uncertain significance may reclassified as being benign (not clinically important) or may eventually be found to be associated with disease phenotype. Therefore, it is important for the person who is tested to keep in touch with the health care provider to ensure that they receive updates if any new information on the variant is learned.
C. Negative Result.
A negative test result means that the laboratory did not find the specific disease linked variant on list of genes that the test was designed to detect. Therefore, patient does not have a genetic variation associated with diabetes mellitus disorders, in the genes tested by the Diabetes genetic testing panel.
Purpose of the Diabetes genetic test:
The Diabetes genetic testing panel may be appropriate for anyone who has a personal or family history of type I or II diabetes mellitus disorders, particularly if those conditions affect more than one individual in the family, experiencing complications of diabetes and long-term disabilities. This panel can help confirm a diagnosis and guide the course of treatment. Patients with type I or II diabetes mellitus disorders can benefit from supplement therapies or go on preventive strategies. Diagnosis through genetic testing can help with the development of a management plan. The Diabetes genetic testing panel would help physicians to establish or confirm the appropriate diagnosis. By confirming diagnosis, the Diabetes genetic testing panel help to identify risks for additional related symptoms, and assist in modifying lifestyle changes.
Clinical Utility:
The Diabetes genetic testing panel establish or confirm the appropriate diagnosis, identify risks for additional related symptoms, result in more personalized treatment and symptom management, inform family members about their own risk factors, connect patients to relevant resources and support, provide options for family planning.
Method:
The test looks for inherited genetic variations (germline mutations) associated with type I or II diabetes. Genes are instructions, written in DNA, for building protein molecules. Different people can have different versions of the same gene. Each version has a slightly different DNA sequence. Some of these variants affect health, such as those gene variants linked to maturity onset diabetes of the young (MODY).
MODY is a heterogeneous disorder identified by non-insulin-dependent diabetes diagnosed at a young age (usually under 25 years). It carries an autosomal dominant transmission and does not involve autoantibodies as in T1DM. Several genes have implications in this disease, including mutations to hepatocyte nuclear factor-1-alpha (HNF1A) and the glucokinase (GCK) gene, which occurs in 52 to 65 and 15 to 32 percent of MODY cases, respectively. The genetics of this disease are still unclear as some patients have mutations but never develop the disease, and others will develop clinical symptoms of MODY but have no identifiable mutation. Testing whether someone carries a harmful (pathogenic) variant in one of these genes can confirm whether a condition is, indeed, the result of an inherited syndrome.
The Diabetes genetic test panel investigates a panel of genes (listed below) for the presence of genetic changes compared to human reference (variants) that are linked to diabetes mellitus conditions.
Express Gene™ Maturity Onset Diabetes of the Young (MODY), and Diabetes Mellitus (Diabetes) Panel is a Laboratory Developed Test (LDT) validated at Express Gene Molecular Diagnostics Laboratory, using Twist Exome 2.0 and Illumina NovaSeq6000 Next Generation Sequencing (NGS) Platform. This test has not been cleared or approved by the FDA.
Limitations of Testing:
This test is designed to detect individuals with a germline pathogenic variant. Repeat expansion diseases, large deletions, duplications, and copy number variations are not detectable by next-generation sequencing (NGS) and require different test methodologies. Mutations in the upstream and downstream regulatory regions and mutations outside exons of protein-coding genes are not investigated. Certain types of variants, such as structural rearrangements, inversions, translocations, variants in regions with low complexity, regions with complex architecture, short tandem repeats, or segmental duplications cannot be detected by this method. Additionally, low-level mosaicism, phasing, and regions with matching pseudogenes causing mapping ambiguity can lead to incorrect or insufficient variant calling.
If you have any further questions or need more information, feel free to ask!