The newly recognized ataxia-ocular apraxia 1 (AOA1; MIM 208920) is the most frequent cause of autosomal recessive ataxia in Japan and is second only to Friedreich ataxia in Portugal. It shares several neurological features with ataxia-telangiectasia, including early onset ataxia, oculomotor apraxia and cerebellar atrophy, but does not share its extraneurological features (immune deficiency, chromosomal instability and hypersensitivity to X-rays). AOA1 is also characterized by axonal motor neuropathy and the later decrease of serum albumin levels and elevation of total cholesterol. We have identified the gene causing AOA1 and the major Portuguese and Japanese mutations. This gene encodes a new, ubiquitously expressed protein that we named aprataxin. This protein is composed of three domains that share distant homology with the amino-terminal domain of polynucleotide kinase 3'- phosphatase (PNKP), with histidine-triad (HIT) proteins and with DNA-binding C2H2 zinc-finger proteins, respectively. PNKP is involved in DNA single-strand break repair (SSBR) following exposure to ionizing radiation and reactive oxygen species. Fragile-HIT proteins (FHIT) cleave diadenosine tetraphosphate, which is potentially produced during activation of the SSBR complex. The results suggest that aprataxin is a nuclear protein with a role in DNA repair reminiscent of the function of the protein defective in ataxia-telangiectasia, but that would cause a phenotype restricted to neurological signs when mutant.

Ataxia with oculomotor apraxia (AOA) is characterized by early-onset cerebellar ataxia, ocular apraxia, early areflexia, late peripheral neuropathy, slow progression, severe motor handicap, and absence of both telangiectasias and immunodeficiency. We studied 13 Portuguese families with AOA and found that the two largest families show linkage to 9p, with LOD scores of 4.13 and 3.82, respectively, at a recombination fraction of 0. These and three smaller families, all from northern Portugal, showed homozygosity and haplotype sharing over a 2-cM region on 9p13, demonstrating the existence of both a founding event and linkage to this locus, AOA1, in the five families. Three other families were excluded from this locus, demonstrating nonallelic heterogeneity in AOA. Early-onset cerebellar ataxia with hypoalbuminemia (EOCA-HA), so far described only in Japan, is characterized by marked cerebellar atrophy, peripheral neuropathy, mental retardation, and, occasionally, oculomotor apraxia. Two unrelated Japanese families with EOCA-HA were analyzed and appeared to show linkage to the AOA1 locus. Subsequently, hypoalbuminemia was found in all five Portuguese patients with AOA1 with a long disease duration, suggesting that AOA1 and EOCA-HA correspond to the same entity that accounts for a significant proportion of all recessive ataxias. The narrow localization of AOA1 should prompt the identification of the defective gene.

Objective: Individuals with stroke frequently experience mobility deficits and limited community reintegration. This study aimed to investigate life-space mobility and relevant factors in community-living individuals with stroke. Methods: This was a cross-sectional study of 46 community-dwelling individuals with chronic stroke in Japan (mean age 72.7 ± 7.4 years; mean time post-stroke 63.6 ± 43.3 months; 26 men/20 women). We measured life-space mobility using a Japanese translation of the Life-Space Assessment. The following factors that might affect life-space mobility were assessed: the ability to perform activities of daily living, physical performance, fear of falling, and cognitive function. Results: A total of 41 participants (89.1%) had restricted life-space mobility (Life-Space Assessment score <60 points). A multiple linear regression analysis showed that limitations in activities of daily living, walking speed, and Falls Efficacy Scale-International scores were independently related to Life-Space Assessment scores. This model explained 51.3% of the variance in Life-Space Assessment scores. Conclusions: Most individuals with stroke had restricted life-space mobility. Life-space mobility was associated with the ability to perform activities of daily living, walking speed, and fear of falling. These findings could contribute to the development of rehabilitation interventions for regaining life-space mobility in individuals with stroke.

The Japanese version of the MPOC has good psychometric properties and can be recommended for evaluation of the processes of child rehabilitation in Japan.

The MPOC-SP has good psychometric properties and can be used to identify areas for improvement in the family-centered care provided by multidisciplinary teams in the NICUs.