Type of Mutations: RTT is mainly caused by commonly sporadic (de novo) and rarely familial mutations of MECP2 gene. These mutations, This gene works as a translational regulator which is critical for normal neurodevelopment. Over 95% of classic RTT cases involve MECP2 mutations.
RTT is an X-linked dominant disorder. One copy of the gene is enough to cause the disease. RTT was initially believed to only affect females for years. For fathers that carry mutated X chromosome, their male children never gets the disease, while they inherit the disease 100% to their daughters. But for mothers with such genetic load, both female and male children have 50 % equal chance to have the disease. Some pathogenic variants of MECP2 may also affect males with a wide range of neurological manifestations between much milder cases than classical RTT and severe neonatal encephalopathy making the diagnosis complicated.
This gene is essential for regulating the expression of numerous genes in the brain and beyond, resulting in significant disruptions in cellular function that can lead to various multi-systemic comorbidities. Some of the affected molecules are vital for cell differentiation, communication, and neural circuitry, while others are crucial for energy metablism.
MECP2