A family with two female siblings with compound heterozygous FMR1 premutation alleles


  • F. T. is a non-paid collaborator with Asuragen, Inc. She has a patent for the detection of FMR1 allele size and category using the CGG linker PCR-based approach. R. H. has received funding for treatment trials in fragile X syndrome or autism from Novartis, Roche, Seaside Therapeutics, Curemark, Forest Pharmaceuticals, and the National Fragile X Foundation. D. H. received support from Novartis, Roche, and Seaside Therapeutics for clinical trials in fragile X syndrome. K. B., R. L., A. S., and C. Y. have no conflicts of interest to disclose.


Premutation alleles (55–200 CGG repeats) of the fragile X mental retardation (FMR1) gene have been linked to various types of clinical involvement ranging from mood and anxiety disorders to immunological disorders and executive function deficits. Carrier females typically have a premutation allele and a normal allele (<55 CGG repeats). Although rare, seven cases of females that carry two expanded alleles (compound heterozygous premutation) have been reported. Here, we report on four members of a family including two compound heterozygous premutation sisters with similar CGG allele sizes, affected with different levels of clinical severity.