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

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.

Neuropathological, clinical and molecular pathology in female fragile X premutation carriers with and without FXTAS.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder associated with premutation alleles of the fragile X mental retardation 1 (FMR1) gene. Approximately 40% of older male premutation carriers, and a smaller proportion of females, are affected by FXTAS; due to the lower penetrance the characterization of the disorder in females is much less detailed. Core clinical features of FXTAS include intention tremor, cerebellar gait ataxia and frequently parkinsonism, autonomic dysfunction and cognitive deficits progressing to dementia in up to 50% of males. In this study, we report the clinical, molecular and neuropathological findings of eight female premutation carriers. Significantly, four of these women had dementia; of the four, three had FXTAS plus dementia. Post-mortem examination showed the presence of intranuclear inclusions in all eight cases, which included one asymptomatic premutation carrier who died from cancer. Among the four subjects with dementia, three had sufficient number of cortical amyloid plaques and neurofibrillary tangles to make Alzheimer's disease a highly likely cause of dementia and a fourth case had dementia with cortical Lewy bodies. Dementia appears to be more common than originally reported in females with FXTAS. Although further studies are required, our observation suggests that in a portion of FXTAS cases there is Alzheimer pathology and perhaps a synergistic effect on the progression of the disease may occur.

Development of a Chinese-Indian hybrid (Chindian) rhesus macaque colony at the California National Primate Research Center by introgression.

BACKGROUND: Fullbred Chinese and Indian rhesus macaques represent genetically distinct populations. The California National Primate Research Center introduced Chinese founders into its Indian-derived rhesus colony in response to the 1978 Indian embargo on exportation of animals for research and the concern that loss of genetic variation in the closed colony would hamper research efforts. The resulting hybrid rhesus now number well over a thousand animals and represent a growing proportion of the animals in the colony. METHODS: We characterized the population genetic structure of the hybrid colony and compared it with that of their pure Indian and Chinese progenitors. RESULTS: The hybrid population contains higher genetic diversity and linkage disequilibrium than their full Indian progenitors and represents a resource with unique research applications. CONCLUSIONS: The genetic diversity of the hybrids indicates that the strategy to introduce novel genes into the colony by hybridizing Chinese founders and their hybrid offspring with Indian-derived animals was successful.