Friedreich ataxia in Acadian families from eastern Canada: Clinical diversity with conserved haplotypes

Journal Article · Fri Sep 06 04:00:00 EDT 1996 · American Journal of Medical Genetics

DOI:https://doi.org/10.1002/(SICI)1096-8628(19960906)64:4<594::AID-AJMG13>3.3.CO;2-P· OSTI ID:518171

Richter, A; Poirier, J; Mercier, J ^[1]

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1. Hopital Sainte-Justine, Montreal (Canada); and others

The gene for Friedreich ataxia (FRDA), an autosomal-recessive neurodegenerative disease, remains elusive. The current candidate region of about 150 kb lies between loci FR2 and F8101 near the D9S15/D9S5 linkage group at 9q13-21.1. Linkage homogeneity between classical FRDA and a milder, slowly progressive Acadian variant (FRDA-Acad) has been demonstrated. An extended D9S15-D9S5 haplotype (C6) predominates in FRDA-Acad chromosomes from Louisiana. We studied 10 Acadian families from New Brunswick, Canada. In eight families, affected individuals conformed to the clinical description of FRDA-Acad; in one, 2 sibs presented with spastic ataxia (SPA-Acad). In the last family, 2 sibs had FRDA-Acad, and one had SPA-Acad. We found that SPA-Acad is linked to the FRDA gene region. The C6 haplotype and a second major haplotype (137) were identified. The same ataxia-linked haplotypes segregated with both FRDA-Acad and SPA-Acad in two unrelated families. The parental origins of these haplotypes were different. Our observation of different phenotypes associated with the same combination of haplotypes may point to the influence of the parent of origin on gene expression, indicate the effect of modifier genes, or reflect the presence of different mutations on the same haplotype. Our findings underline the need to investigate families with autosomal-recessive ataxias for linkage to the FRDA region, despite lack of key diagnostic manifestations such as cardiomyopathy or absent deep-tendon reflexes. 28 refs., 4 figs., 3 tabs.

• OSTI ID: 518171
• Journal Information: American Journal of Medical Genetics, Journal Name: American Journal of Medical Genetics Journal Issue: 4 Vol. 64; ISSN 0148-7299; ISSN AJMGDA
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
BIOLOGICAL MARKERS
CANADA
GENE MUTATIONS
GENE RECOMBINATION
GENE REGULATION
GENES
GENETIC MAPPING
GENETICS
HEREDITARY DISEASES
HUMAN CHROMOSOME 9
NERVOUS SYSTEM DISEASES
PATIENTS
PHENOTYPE
RECESSIVE MUTATIONS