Giant axonal neuropathy (GAN) is a rare autosomal recessive disorder described as a symmetrical distal neuropathy, with peripheral axons dilated by accumulation of 10 nm neurofilaments (NF) and a severe course of the disease. The observation of kinky or curly hairs is not a constant finding. The GAN1 locus was localized by homozygosity mapping to chromosome 16 q24.1 in a 3 (4) cM interval flanked by the markers D16S3073 and D16S505 (D16S511) in three non-related Tunisian families, showing a genetic homogeneity in these families. Two point lod-score calculation between the linked haplotype and the disease locus was 14.2 at theta(max) = 0. The patients share a slow course of the disease. The differences in the course of the disease between Tunisian and non-Tunisian patients suggest a possible genetic heterogeneity, which is why the present linkage has been referred to as GAN1. The biochemical defect in GAN1 should help to understand the mechanisms involved in NF accumulations as in other neurological diseases (ALS, SMA).
OBJECTIVE: To report the clinical findings and the genetic linkage mapping of an autosomal recessive cerebellar ataxia associated to peripheral neuropathy, showing an early onset cerebellar ataxia with retained tendon reflexes (EOCA) phenotype. BACKGROUND: EOCA is a clinical syndrome delimited by Harding distinguished from Friedreich's ataxia (FA) mainly by the preservation of tendon reflexes. Molecular genetic study of patients with EOCA has demonstrated genetic heterogeneity. A form of autosomal recessive spastic ataxia has been described in Charlevoix Saguenay area in Quebec (ARSACS); the gene responsible has been mapped to chromosome 13q. METHODS: Genetic linkage analysis was performed on 18 members of a large family including 8 of 9 members with EOCA. After exclusion of FA and ataxia with vitamin E deficiency loci as well as loci of autosomal dominant cerebellar ataxias, we performed a linkage analysis to markers of 13q11‐12 region. RESULTS: The 9 affected members of this family showed stereotyped clinical features with cerebellar ataxia, pyramidal syndrome, and a variable degree of axonal peripheral neuropathy. Linkage was detected between the disease locus and the microsatellite marker D13S232. Surrounding markers to D13S232 confirmed the linkage and showed the homozygosity of the affected members. CONCLUSION: The family reported here showed the same locus as autosomal recessive spastic ataxia Charlevoix Saguenay disease.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.