Investigation of Recessive Ataxia Loci in Patients with Young Age of Onset

Abstract

Autosomal recessive cerebellar ataxias are a phenotypically and genetically heterogeneous group of diseases. Major forms can be distinguished on the basis of clinical signs, age of onset, biochemical parameters or genotypes. To develop rational diagnostic strategies, phenotypic information, e.g., age of onset combined with population-specific disease frequencies could be highly favourable. We tested this hypothesis for single candidate loci and mutations in North European ataxia patients with juvenile and early adult onset. While we could prove that Friedreich ataxia (FRDA) is frequent in Germany, only few patients with ataxia-oculomotor apraxia type 1 (AOA1) and type 2 (AOA2) were diagnosed. The frequency of the mitochondrial recessive ataxia syndrome (MIRAS) and the infantile onset spinocerebellar ataxia (IOSCA) in this population remains unknown since no case with the common mutation of the corresponding gene was detected.

FRDA - AOA1 - AOA2 - MIRAS - IOSCA

References

• 1 Campuzano V, Montermini L, Molto MD, Pianese L, Cossee M, Cavalcanti F. et al . Friedreich's ataxia: Autosomal recessive disease caused by an intronic GAA triplet repeat expansion.  Science. 1996;  271 1423-1427
• 2 Habeck M, Zühlke C, Bentele KHP, Unkelbach S, Kress W, Bürk K. et al . Aprataxin mutations are a rare cause of early onset ataxia in Germany.  J Neurol. 2004;  251 591-594
• 3 Hakonen AH, Davidzon G, Salemi R, Bindoff LA, Van Goethem G, Dimauro S. et al . Abundance of the POLG disease mutations in Europe, Australia, New Zealand, and the United States explained by single ancient European founders.  Eur J Hum Genet. 2007;  , epub Apr 11
• 4 Hakonen AH, Heiskanen S, Juvonen V, Lappalainen I, Luoma PT, Rantamaki M. et al . Mitochondrial DNA polymerase W748S mutation: a common cause of autosomal recessive ataxia with ancient European origin.  Am J Hum Genet. 2005;  77 430-441
• 5 Ber I Le, Bouslam N, Rivaud-Pechoux S, Guimaraes J, Benomar A, Chamayou C. et al . Frequency and phenotypic spectrum of ataxia with oculomotor apraxia 2: a clinical and genetic study in 18 patients.  Brain. 2004;  127 759-767
• 6 Moreira MC, Barbot C, Tachi N, Kozuka N, Uchida E, Gibson T. et al . The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT/Zn-finger protein aprataxin.  Nat Genet. 2001;  29 189-193
• 7 Moreira MC, Klur S, Watanabe M, Nemeth AH, Ber I Le, Moniz JC. et al . Senataxin, the ortholog of a yeast RNA helicase, is mutant in ataxia-ocular apraxia.  Nat Genet. 2004;  36 225-227
• 8 Nikali K, Suomalainen A, Saharinen J, Kuokkanen M, Spelbrink JN, Lonnqvist T. et al . Infantile onset spinocerebellar ataxia is caused by recessive mutations in mitochondrial proteins Twinkle and Twinky.  Hum Mol Genet. 2005;  14 2981-2990
• 9 Zühlke Ch, Dalski A, Habeck M, Straube K, Hedrich K, Hoeltzenbein M. et al . Extension of the mutation spectrum in Friedreich's ataxia: Detection of an exon deletion and novel missense mutations.  Eur J Hum Genet. 2004;  12 979-982

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