This is a mechanism module, not a disease entry. Disorder files should refer to its nodes via conforms_to using "fame_pentanucleotide_repeat_rna_toxicity#<Node Name>". The module is intentionally conservative: it treats TTTCA-containing repeat RNA toxicity as the shared core mechanism and does not require host-gene loss of function or repeat-associated non-AUG translation.
Pathogenic TTTCA-Containing Pentanucleotide Repeat Expansion
trigger
Pathogenic FAME alleles are intronic pentanucleotide repeat expansions in which elongated TTTTA tracts contain inserted TTTCA segments. TTTTA-only expansions are generally regarded as nonpathogenic, whereas the presence of TTTCA insertions tracks with disease.
Downstream
-
UUUCA Repeat RNA Toxicity
UUUCA Repeat RNA Toxicity
central effector
Transcription of the expanded alleles can produce UUUCA repeat-containing RNA that accumulates in nuclear foci and is thought to drive RNA-mediated toxicity largely independently of the host gene's normal function.
Downstream
-
Cerebellocortical Circuit Dysfunction
Cerebellocortical Circuit Dysfunction
amplifier
Postmortem, neurophysiological, and imaging studies indicate combined dysfunction of the cerebral cortex and cerebellum, especially Purkinje-cell and cerebellar network involvement that may amplify the cortical phenotype.
Downstream
-
Cortical Hyperexcitability and Seizure Susceptibility
Cortical Hyperexcitability and Seizure Susceptibility
effector
The final common network state is cortical hyperexcitability, manifested as cortical-origin myoclonus, enlarged long-loop responses, photosensitivity, and susceptibility to generalized epileptic seizures.