ANALYSIS OF ALDEHYDE OXIDASE AND XANTHINE DEHYDROGENASE OXIDASE AS POSSIBLE CANDIDATE GENES FOR AUTOSOMAL RECESSIVE FAMILIAL AMYOTROPHIC-LATERAL-SCLEROSIS

Recently, point mutations in superoxide dismutase 1 (SOD1) have been s hown to lead to a subset of autosomal dominantly inherited familial am yotrophic lateral sclerosis (ALS). These findings have led to the hypo thesis that defects in oxygen radical metabolism may be involved in th e pathogenesis of ALS. Therefore, we decided to analyze other enzymes involved in oxygen radical metabolism for possible involvement in othe r forms of ALS. We report here analysis of two genes encoding the moly bdenum hydroxylases aldehyde oxidase (AO) and xanthine dehydrogenase/o xidase (XDH) for involvement in ALS. Of particular interest, one gene identified as encoding aldehyde oxidase is shown to map to 2q33, a reg ion recently shown to contain a gene responsible for a familial form o f ALS with autosomal recessive inheritance (FALS-AR). The AO gene appe als to be located within 280, 000 bp of simple sequence repeat marker D2S116, which shows no recombination with the FALS-AR locus. The AO ge ne is highly expressed in glial cells of human spinal cord. In additio n, we mapped a gene for XDH to 2p22, a region previously shown to cont ain a highly homologous but different form of XDH. Neither of these XD H genes appears to be highly expressed in human spinal cord. This evid ence suggests that AO may be a candidate gene for FALS-AR.