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Malaysian Siblings with Friedreich Ataxia and Chorea: A Novel Deletion in the Frataxin Gene

Published online by Cambridge University Press:  02 December 2014

Siân D. Spacey ,
Blazej I. Szczygielski ,
Sean P. Young ,
Juliette Hukin ,
Kathy Selby  and
Terrance P. Snutch
Siân D. Spacey
Affiliation:
Division of Neurology and the Biotechnology Laboratory and the Brain Research Center, University of British Columbia, Vancouver, B.C., Canada
Blazej I. Szczygielski
Affiliation:
Biotechnology Laboratory, University of British Columbia, Vancouver, B.C., Canada
Sean P. Young
Affiliation:
Dept. of Medical Genetics, B.C. Children's Hospital, Vancouver, B.C., Canada
Juliette Hukin
Affiliation:
Dept. of Pediatrics, B.C. Children's Hospital, Vancouver, B.C., Canada
Kathy Selby
Affiliation:
Dept. of Pediatrics, B.C. Children's Hospital, Vancouver, B.C., Canada
Terrance P. Snutch
Affiliation:
Biotechnology Laboratory, University of British Columbia, Vancouver, B.C., Canada
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Abstract

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Background:

Friedrich ataxia (FRDA1) is most often the result of a homozygous GAA repeat expansion in the first intron of the frataxin gene (FRDA gene). This condition is seen in individuals of European, North African, Middle Eastern and Indian descent and has not been reported in Southeast Asian populations. Approximately 4% of FRDA1 patients are compound heterozygotes. These patients have a GAA expansion on one allele and a point mutation on the other and have been reported to have an atypical phenotype.

Objective:

To describe a novel dinucleotide deletion in the FRDA gene in two Malaysian siblings with FRDA1.

Setting:

Tertiary referral university hospital setting. Patients and

Methods:

A previously healthy 10-year-old Malaysian boy, presented with fever, lethargy, headaches, dysarthria, dysphagia, vertigo and ataxia which developed over a one week period. His neurological exam revealed evidence of dysarthria and ataxia, mild generalized weakness and choreoform movements of the tongue and hands. His reflexes were absent and Babinski sign was present bilaterally. A nine-year-old sister was found to have mild ataxia but was otherwise neurologically intact.

Results:

Molecular genetic studies demonstrated that both siblings were compound heterozygotes with a GAA expansion on one allele and a novel dinucleotide deletion on the other allele.

Conclusion:

We describe a novel dinucleotide deletion in the first exon of the FRDA gene in two siblings with FRDA1. Additionally this is the first report of FRDA1 occurring in a family of southeast Asian descent, it demonstrates intrafamilial phenotypic variability, and confirms that atypical phenotypes are associated with compound heterozygosity.

Type
Research Article
Information
Canadian Journal of Neurological Sciences , Volume 31 , Issue 3 , August 2004 , pp. 383 - 386
Copyright
Copyright © The Canadian Journal of Neurological 2004

References

1.Harding, AE, Hewer, RL.The heart disease of Friedreich ataxia: a clinical and electrocardiographic study of 115 patients with an analysis of serial electrocardiographic changes in 30 cases. Q J Med 1983;52:489–502.Google Scholar
2.Harding, AE.Friedreich ataxia. A clinical and genetic study of 90 families with an analysis of early diagnostic criteria and interfamilial clustering of clinical features. Brain 1981;104:589–620.Google Scholar
3.Chamberlain, S, Shaw, J, Rowland, A, et al.Mapping of mutation causing Friedreich ataxia to human chromosome 9. Nature 1988;334:248–250.Google Scholar
4.Babcock, M, de Silva, D, Oaks, R, et al.Regulation of mitochondrial iron accumulation by Yfh1p, a putative homolog of frataxin. Science 1997;276:1709–1712.Google Scholar
5.Campuzano, V, Montermini, L, Molto, MD, et al.Friedreich ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science 1996;271:1423–1427.Google Scholar
6.Montermini, L, Kish, SJ, Jiralerspong, S, et al.Somatic mosaicism for Friedreich ataxia GAA triplet repeat expansions in the central nervous system. Neurology 1997;49:606–610.Google Scholar
7.Zhu, D, Burke, C, Leslie, A, et al.Friedreich ataxia with chorea and myoclonus caused by a compound heterozygosity for a novel deletion and the trinucleotide GAAexpansion. Mov Disord 2002 2002;17(3):585–589.Google Scholar
8.McCormack, ML, Guttmann, RP, Schumann, M, et al.Frataxin point mutations in two patients with Friedreich ataxia and unusual clinical features. J Neurol Neurosurg Psychiatry 2000;68:661–664.CrossRefGoogle ScholarPubMed
9.Hanna, MG, Davis, MB, Sweeney, MG, et al.Generalized chorea in two patients harboring the Friedreich ataxia gene trinucleotide repeat expansion. Mov Disord 1998;13(2):339–340.Google Scholar
10.Durr, A, Cossee, M, Agid, Y, et al.Clinical and genetic abnormalities in patients with Friedreich ataxia. N Eng J Med 1996;335:1169–1175.Google Scholar
11.Machkhas, H, Bidichandani, SI, Patel, PI.A mild case of Friedreich ataxia: lymphocyte and sural nerve analysis for GAA repeat length reveals somatic mosaicism. Muscle Nerve 1998;21:390–393.Google Scholar
12.Labuda, M, Labuda, C, Miranda, C, et al.Unique origin and specific ethnic distribution of the Friedreich ataxia GAA expansion. Neurology 2000;54:2322–2324.CrossRefGoogle ScholarPubMed
13.Cossee, M, Durr, A, Schmitt, M, et al.Friedreich ataxia: point mutations and clinical presentation of compound heterozytgotes. Ann Neur 1999; 45:200–206.Google Scholar
14.McCabe, DJH, Ryan, F, Moore, DP, et al.Typical Friedreich ataxia without GAA expansions and GAA expansions without typical Friedreich ataxia[published correction appears in J Neurol 2000;247:483]. J Neurol 2000;247:346–355.CrossRefGoogle Scholar
15.Kellett, MW, Fletcher, NA, Wood, NW, et al.Trinucleotide (GAA)n repeat expansion in two families with Friedreich ataxia with retained reflexes. J Neurol Neurosurg Psychiatry 1997;63:780–783.Google Scholar
16.McCabe, DJH, Wood, NW, Ryan, F, et al.Intrafamilial Phenotypic variability in Friedreich ataxia associated with a G130Vmutation in the FRDA gene. Arch Neurol 2002;59:296–300.CrossRefGoogle ScholarPubMed