digenic disease

What is Digenic Disease?

Digenic disease, also known as digenic inheritance, is a form of genetic disorder that arises from the interaction between variants in two different genes [1][2]. This type of disease is considered the simplest form of oligogenic disease, where the presence of pathogenic variants in both genes is required for the disease to manifest [3].

Key Characteristics

• Two Gene Interaction: Digenic diseases result from the additive effect of mutations in two separate genes, leading to a disease or phenotype [4].
• Simplest Form of Oligogenic Disease: Digenic inheritance is considered the simplest form of oligogenic disease, where multiple genes interact to produce a disease phenotype [5].
• Mono-allelic Mutations: True digenic inheritance occurs when two mono-allelic mutations, on separate genes, are co-present in an individual, leading to the manifestation of the disease [6].

Examples and Studies

• The DIDA (DIgenic diseases DAtabase) is a novel database that provides detailed information on genes and associated genetic variants related to digenic diseases [7].
• A study by Mukherjee et al. (2021) aimed to develop a machine learning classifier to identify digenic disease gene pairs, which have different attributes than non-digenic disease gene pairs [8].

Inheritance Pattern

Digenic disorders often follow a simple Mendelian inheritance pattern, with another mode of inheritance contributing to the disease phenotype [9]. This complex interaction between genes can lead to a wide range of diseases and phenotypes.

References:

[1] AA Schäffer (2013) - Cited by 222 [2] N Moreno-Ruiz (2022) - Cited by 7 [3] Aug 26, 2021 [4] CM Neuhofer (2024) [5] Aug 15, 2023 [6] AM Gazzo (2016) - Cited by 112 [7] AA Schäffer (2013) - Cited by 222 [8] S Mukherjee (2021) - Cited by 37 [9] Jan 1, 2018

Digenic diseases are a group of disorders caused by the interaction of two or more genes, leading to a range of symptoms and signs that can vary widely depending on the specific disease.

Common Signs and Symptoms:

• Abnormality of blood and blood-forming tissues, including anemia, bone marrow hypocellularity, and thrombocytopenia [1]
• Abnormality of head or neck, which may include developmental delays, obesity, retinal defects, and hypogonadism [3]

Specific Signs and Symptoms:

• Renal anomalies
• Polydactyly (extra fingers or toes)
• Obesity
• Retinal defects
• Developmental delay
• Hypogonadism (underdeveloped reproductive organs)

Other Possible Signs and Symptoms:

• Muscle weakness and wasting, particularly in the facioscapulohumeral muscular dystrophy [9]
• Forearm weakness and wrist extension weakness
• Abdominal and distal lower limb muscle weakness, particularly in the tibialis anterior muscle

It's essential to note that the specific signs and symptoms of digenic diseases can vary widely depending on the individual case and the genes involved. A comprehensive diagnosis by a medical professional is necessary for an accurate understanding of the disease.

References: [1] CM Neuhofer (2024) - Known digenic disease causes show a range of pathomechanisms underlying digenic interplay, including direct and indirect gene product interactions. [3] AA Schäffer (2013) - The phenotype of BBS typically includes six aspects: renal anomalies, polydactyly, obesity, retinal defects, developmental delay, and hypogonadism. [9] by CM Neuhofer · 2024 — Digenic inheritance is the simplest instance of a non-Mendelian disorder, characterized by the functional interplay of variants in two disease-contributing genes.

Understanding Digenic Diseases

Digenic diseases are conditions caused by mutations in two or more genes, rather than a single gene. These diseases can be challenging to diagnose due to their complex genetic basis.

Diagnostic Challenges

The diagnostic process for digenic diseases is often complicated by the fact that these conditions can be caused by multiple combinations of genetic variants. This makes it difficult to identify a specific test or marker that can accurately diagnose the condition.

Current Diagnostic Approaches

Several studies have proposed various approaches for diagnosing digenic diseases, including:

• Genome-wide association studies (GWAS): These studies analyze genetic variations across the entire genome to identify associations with disease. [1]
• Whole-exome sequencing (WES): This approach involves sequencing all protein-coding regions of the genome to identify potential disease-causing variants. [2]
• Machine learning algorithms: Researchers have developed machine learning models that can predict digenic disease risk based on genetic data. [3]

Emerging Diagnostic Tools

New diagnostic tools are being developed to improve the detection of digenic diseases, including:

• Digenic disease databases: These databases collect and analyze information on genes and associated genetic variants related to digenic diseases. [4]
• Predictive models: Researchers have proposed predictive models that can identify individuals at risk for digenic diseases based on their genetic profile. [5]

Future Directions

The development of more accurate and efficient diagnostic tests is crucial for improving the diagnosis and management of digenic diseases. Future research should focus on:

• Improving genome-wide association studies: Enhancing GWAS to better detect associations between genetic variants and disease.
• Developing new machine learning algorithms: Creating more sophisticated machine learning models that can accurately predict digenic disease risk.
• Expanding digenic disease databases: Increasing the scope and accuracy of databases related to digenic diseases.

References:

[1] Kerner, G. (2020). A statistical test for detecting digenic inheritance in WES data. [2] Mukherjee, S. (2021). DiGePred: A machine learning-based classifier for predicting digenic disease risk. [3] Moreno-Ruiz, N. (2022). Assessing the statistical power of detecting associations between digenic combinations and disease. [4] Gazzo, A. M. (2016). DIDA: A novel database for digenic diseases. [5] Ben-Mahmoud, A. (2023). Accurate diagnosis and prognosis in presumed monogenic disorders.

Note: The numbers in square brackets refer to the corresponding search results provided in the context.

Digenic diseases are caused by an interaction between variants in two genes, which can lead to various health issues. When it comes to treating digenic diseases, the approach is often similar to that of monogenic diseases, but with a focus on addressing the combined effects of the two mutated genes.

Early Treatment and Family Screening

Individuals with digenic variants should be treated early in life, as mentioned by [3] J Savige · 2022. It's also essential to identify and treat affected family members, as they may carry similar genetic mutations. Furthermore, those with digenic variants should be dissuaded from having children, as the risk of passing on the mutated genes is higher.

Treatment Strategies

While there isn't a specific "digenic disease treatment" available, the approach often involves managing symptoms and addressing the underlying genetic causes. This can include:

• Gene therapy: In some cases, gene therapy may be used to correct or replace the faulty genes responsible for the digenic disease.
• Pharmacological interventions: Medications may be prescribed to alleviate symptoms or slow disease progression.
• Lifestyle modifications: Patients with digenic diseases may need to make significant lifestyle changes, such as dietary adjustments or regular exercise, to manage their condition.

Research and Future Directions

As our understanding of rare disease genetics evolves, researchers are exploring new approaches to treating digenic diseases. For instance, studies have shown that liposome-RNP delivery can be used to recover hearing in individuals with dominant mutations in OHC genes [2] by Y Tao · 2023. This suggests that targeted therapies may become available for specific digenic conditions.

Challenges and Considerations

Investigating the possibility of digenic and oligogenic mutations in presumed monogenic disorders challenges the traditional notion of rare disease genetics, as mentioned by [4] A Ben-Mahmoud · 2023. This highlights the need for a more nuanced understanding of genetic diseases and their treatment.

References:

[1] CM Neuhofer · 2024 [2] Y Tao · 2023 [3] J Savige · 2022 [4] A Ben-Mahmoud · 2023

Differential Diagnosis of Digenic Diseases

Digenic diseases, also known as digenic inheritance, are a type of genetic disorder caused by mutations in two unlinked genes. The differential diagnosis of digenic diseases can be challenging due to their complex genetic mechanisms.

• Monogenic vs. Digenic Inheritance: One key aspect of differential diagnosis is distinguishing between monogenic and digenic inheritance patterns. Monogenic diseases are caused by mutations in a single gene, whereas digenic diseases result from the combination of mutations in two unlinked genes.
  • According to source 3, either the inheritance can be digenic or there can be two different diseases in the pedigree each caused by a different gene. This highlights the importance of considering both monogenic and digenic possibilities when diagnosing genetic disorders.
• Genetic Factors: The differential diagnosis of digenic diseases also involves identifying the specific genetic factors contributing to the disease phenotype. For instance, source 6 notes that in digenic inheritance, mutations in each of two unlinked genes are present in a single individual, and the combination of the two genetic hits causes a disease.
  • This suggests that understanding the specific genetic mechanisms underlying digenic diseases is crucial for accurate diagnosis and treatment.
• Differential Diagnosis: The differential diagnosis of digenic diseases can be complex due to the involvement of multiple genes and pathways. However, by considering the genetic factors and inheritance patterns, healthcare professionals can narrow down the possible causes and develop an effective diagnostic plan.

References:

1. Source 3
2. Source 6