SNP Shot: Genomic Insights

Common variable immunodeficiency (CVID) is an immune system disorder that makes individuals highly vulnerable to infections. Those with CVID are prone to recurring infections, especially in the lungs, sinuses, and ears, often caused by bacteria, but sometimes by viruses. Pneumonia is a frequent complication. Repeated infections can eventually lead to chronic lung problems. Furthermore, individuals may suffer from gastrointestinal issues, like inflammation or infection, leading to diarrhea and weight loss. Some CVID patients experience enlarged lymph nodes (lymphadenopathy) or an enlarged spleen (splenomegaly) due to immune cell buildup. These immune cells can also form granulomas, small lumps, in other organs.

Approximately 25% of individuals with CVID develop autoimmune disorders, where the immune system mistakenly attacks the body's own tissues. Blood cells are commonly targeted. Examples include immune thrombocytopenia, a bleeding disorder due to low platelet counts, and autoimmune hemolytic anemia, characterized by the premature destruction of red blood cells. Rheumatoid arthritis is another possible autoimmune condition. Moreover, people with CVID face a higher risk of certain cancers, such as non-Hodgkin lymphoma (a cancer of immune cells) and, less frequently, stomach (gastric) cancer.

Symptoms of CVID can appear anytime from childhood to adulthood, with most diagnoses occurring in the twenties or thirties. Life expectancy for individuals with CVID varies based on the severity and frequency of their illnesses. However, most people with CVID live into adulthood.

CVID encompasses various subtypes, each linked to a specific genetic cause. Even within the same subtype, the signs and symptoms can differ among individuals.

Inheritance:

Most CVID cases are sporadic, arising in individuals without a family history of the condition. These cases are likely due to a complex interplay of environmental and genetic factors. Rarely, CVID is inherited in an autosomal recessive manner, meaning both copies of a specific gene must be mutated. In these cases, both parents carry one copy of the mutated gene but usually don't show symptoms. In a few cases, CVID follows an autosomal dominant inheritance pattern, where a mutation in just one copy of a gene is enough to cause the disorder.

When CVID is caused by mutations in the TNFRSF13B gene, it's often sporadic, resulting from a new mutation during reproductive cell (egg or sperm) formation or early embryonic development. Inherited TNFRSF13B mutations can lead to either autosomal dominant or autosomal recessive CVID.

It's important to note that not everyone who inherits a gene mutation associated with CVID will develop the condition. Often, affected children have an unaffected parent who carries the same mutation. This suggests that additional genetic or environmental factors are necessary for the disorder to manifest.