抄録
Fragile X mental retardation 1 (FMR1) premutation associated phenotypes have been explored extensively since the molecular mechanism emerged involving elevated FMR1 messenger ribonucleic acid (mRNA) levels. Lowered fragile X mental retardation protein (FMRP) can also occur which may have an additive effect to the high levels of mRNA leading to neurodevelopmental problems and psychopathology. This paper was aimed to review psychosis and catatonia in premutation carriers, express the role of elevated FMR1 mRNA and lowered FMRP in the phenotype of carriers and present a case of psychosis and catatonia in a carrier. This case also demonstrates additional genetic and environmental factors which may also affect the phenotype. We review the literature and report an exemplary case of a 25 year old male premutation carrier with elevated FMR1 mRNA, low FMRP, a cytochrome P450 family 2 subfamily D polypeptide 6 (CYP2D6)*2xN mutation and a perinatal insult. This patient developed an autism spectrum disorder, psychosis, catatonia with subsequent cognitive decline after electro-convulsive therapy (ECT) for his catatonia. He had a premutation of 72 CGG repeat in FMR1, FMR1 mRNA level that was over 2.4 times normal and FMRP level at 18% of normal, and additionally, a CYP2D6 allelic variant which leads to ultrarapid metabolism (UM) of medication. There is an overlapping pathophysiological mechanism of catatonia and fragile X-associated premutation phenotypes including autism and psychosis. This case demonstrates the shared phenotype and the overlap of the pathophysiological mechanisms that can influence the intervention. Multiple genetic and environmental hits can lead to more significant involvement in premutation carriers.
