Transmission of double FMR1 allelic premutations in a family

Abstract

The fragile X mental retardation 1 (FMR1) gene is the only gene known responsible for fragile X related disorders, including fragile X syndrome (FXS), fragile X-associated primary ovarian insufficiency, and fragile X-associated tremor/ataxia. Although FMR1 premutation carriers are common, double mutations of the FMR1 gene is very rare. To our knowledge, only twelve such reports including twenty-three cases from fourteen families have been documented. We report here another family with a FXS family history in which the proband’s maternal grandmother had compound FMR1 gene premutations and we review twelve published papers associated with double allelic mutations. Our study and literature review indicated that compound premutations may have influences regarding the early onset of fragile X-associated primary ovarian insufficiency and severity of psychiatric issues, and less likely aggravate the cognitive deficits compared with one allele mutant patients. Further detailed studies of similar cases are needed to clarify the profile of double FMR1 premutaions.