Friedreich ataxia (FRDA), the most common autosomal recessive neurodegenerative disease among Europeans and people of European descent, is characterized by an early onset (usually before the age of 25), progressive ataxia, sensory loss, absence of tendon reflexes and pyramidal weakness of the legs. We have recently identified a unique group of patients whose clinical presentations are characterized by autosomal recessive inheritance, early age of onset, FRDA-like clinical presentations and hypoalbuminemia. Linkage to the FRDA locus, however, was excluded. Given the similarities of the clinical presentations to those of the recently described ataxia with oculomotor apraxia (AOA) linked to chromosome 9p13, we confirmed that the disorder of our patients is also linked to the same locus. We narrowed the candidate region and have identified a new gene encoding a member of the histidine triad (HIT) superfamily as the 'causative' gene. We have called its product aprataxin; the gene symbol is APTX. Although many HIT proteins have been identified, aprataxin is the first to be linked to a distinct phenotype.

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Recent studies have described silver- and tau-positive glia and threads in the degenerating lesions of progressive supranuclear palsy. In this study, Gallyas-Braak silver impregnation and several immunohistochemical techniques were employed to examine the distribution of tangles, abnormal glia and threads in the cerebral cortex of nine cases of progressive supranuclear palsy. In addition to neurofibrillary tangles, argentophilic glia and threads were impregnated exclusively by Gallyas-Braak technique. This technique demonstrated two types of glia profiles: tightly coiled intra-cytoplasmic profiles surrounding nuclei (coiled profiles) and thorn-like profiles with radial ramifications (thorn-like profiles). Thorn-like profiles are possibly in astrocytes and were detected in the cerebral cortex, while coiled profiles are possibly in oligodendroglia and were detected both in the cerebral cortex and subcortical white matter. Topographically, many neurofibrillary tangles were constantly seen in the frontal cortex and in the pre-central gyrus. Numerous neurofibrillary tangles were detected in the entorhinal cortex of the two brains. Argentophilic glia and threads were also frequent both in the frontal cortex and the precentral gyrus; however, they were more frequent in the pre-central gyrus that in the frontal cortex in four of the eight cases examined. In two brains, argentophilic threads were distributed widely in the cerebral cortex and white matter except for the temporal cortex. In immunohistochemical studies, argentophilic glia and threads were mostly positive for Tau 2, and a small number of them were weakly positive for ubiquitin and paired helical filament protein. The immunoproperties of these abnormal glia and threads seemed to be virtually identical to those of neurofibrillary tangles.(ABSTRACT TRUNCATED AT 250 WORDS)