Linkage to Chromosome 13q11‐12 of an Autosomal Recessive Cerebellar Ataxia in a Tunisian Family

Abstract

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.

Phenotypic Features and Genetic Findings in Sacsin-Related Autosomal Recessive Ataxia in Tunisia

“…1,2 It was thought that this disease was confined to Charlevoix-Saguenay until the description of the Tunisian family with linkage to the same locus. 5 The clinical, electrophysiological, and nerve biopsy findings of the patients described herein are similar to those described in the first Tunisian family linked to the ARSACS locus and are also comparable to those in the Canadian patients except for some minor differences. 5 In our patients, the age at onset varied from 1 to 20 years, whereas in the Canadian patients, disease onset was reported to occur around walking age (12-18 months).…”

“…5 The clinical, electrophysiological, and nerve biopsy findings of the patients described herein are similar to those described in the first Tunisian family linked to the ARSACS locus and are also comparable to those in the Canadian patients except for some minor differences. 5 In our patients, the age at onset varied from 1 to 20 years, whereas in the Canadian patients, disease onset was reported to occur around walking age (12-18 months). In the Tunisian and Canadian patients, the cerebellar syndrome had been present since the onset of the disease and remained moderate throughout, whereas the pyramidal syndrome worsened, becoming predominant in the later stages.…”

“…The patients described are all of Tunisian descent. Three families (families 1, 3, and 4) originated from and are still living in the center of Tunisia in the same region as the first Tunisian family described by Mrissa et al 5 One family resides in Tunis. The families do not seem to be related, but it is difficult to trace their lineage for more than 3 generations.…”

“…4 Outside of Quebec, only 1 family, fromTunisia,haspreviouslybeenfounddemonstrating linkage to this locus; 9 patients were identified in this family. 5 The objective ofthisstudywastodescribetheclinicalsigns, neurophysiological and nerve biopsy findings, and mutation analysis in 4 new Tunisian families comprising 18 patients.…”