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Huntington disease is a neurodegenerative disorder that involves preferential atrophy in the striatal complex and related subcortical nuclei. In this paper, which is based on a dataset extracted from the PREDICT-HD study, we use statistical shape analysis with deformation markers obtained through Large Deformation Diffeomorphic Metric Mapping of cortical surfaces to highlight specific atrophy patterns in the caudate, putamen, and globus pallidus, at different prodromal stages of the disease. Based on the relation to cortico-basal-ganglia circuitry, we propose that statistical shape analysis, along with other structural and functional imaging studies, may help expand our understanding of the brain circuitry affected and other aspects of the neurobiology of HD, and also guide the most effective strategies for intervention.

Inherited hearing impairment can occur either in the presence of other clinical features (syndromic hearing loss, SHL) or in isolation (non-syndromic hearing loss, NSHL). The latter is more common and is highly heterogeneous. To date, six NSHL loci have been mapped. We report the identification of a seventh locus (DFNA4) on chromosome 19q13 and suggest DM kinase as a possible candidate gene.

Background Chronic alcoholics have increased susceptibility to and severity of infection, which are likely to be a result of impaired immune defense mechanisms. The contribution of dendritic cells (DC) to these immune defense changes is not well understood. Alterations in DC numbers, dendropoiesis, and lifespan have not been specifically studied in vivo in chronic ethanol (EtOH) exposure models. As DC play an essential role in initiating immune responses, alterations in these DC characteristics would help explain changes observed in adaptive immune responses. Methods Mice received 20% EtOH (w/v) in the drinking water for up to 28 weeks, with mouse chow ad libitum. In EtOH-fed and water control mice, DC were enumerated by flow cytometry. The effect of EtOH on DC precursor numbers was determined by differentiation in vitro in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4, and the effect of an EtOH environment on untreated DC differentiation was measured following bone marrow transfer to irradiated hosts. DC turnover rate was also examined by bromodeoxyuridine incorporation and loss. Results The percentage and absolute numbers of DC were decreased in spleen and increased in thymus beginning as early as 4 weeks of EtOH feeding. In addition, the overall cellularity of spleen and thymus were altered by this regimen. However, chronic EtOH consumption did not adversely affect DC precursor numbers, differentiation abilities, or turnover rates. Conclusions Decreased splenic DC numbers observed following chronic murine EtOH consumption are not because of altered DC precursor numbers or differentiation, nor increased DC turnover rate. Similarly, increased thymic DC numbers are not the result of alterations in DC precursor differentiation or turnover rate. Compartment size plays a role in determining splenic and thymic DC numbers following chronic EtOH feeding. EtOH-induced alterations in total DC numbers provide several mechanisms to partially explain why chronic alcoholics have increased susceptibility to infections.

Late-onset non-syndromic hearing impairment is the most common type of neurological dysfunction in the elderly. It can be either acquired or inherited, although the relative impact of heredity on this type of loss is not known. To date, nine different genes have been localized, but none has been cloned. Using an extended American family in which a gene for autosomal dominant late-onset non-syndromic hearing impairment is segregating, we have identified a new locus, DFNA10, on chromosome 6.