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Clinical and genetic abnormalities in patients with Friedreich's ataxia.
N Engl J Med. 1996 Oct 17; 335(16):1169-75.NEJM

Abstract

BACKGROUND

Friedreich's ataxia, the most common inherited ataxia, is associated with a mutation that consists of an unstable expansion of GAA repeats in the first intron of the frataxin gene on chromosome 9, which encodes a protein of unknown function.

METHODS

We studied 187 patients with autosomal recessive ataxia, determined the size of the GAA expansions, and analyzed the clinical manifestations in relation to the number of GAA repeats and the duration of disease.

RESULTS

One hundred forty of the 187 patients, with ages at onset ranging from 2 to 51 years, were homozygous for a GAA expansion that had 120 to 1700 repeats of the trinucleotides. About one quarter of the patients, despite being homozygous, had atypical Friedreich's ataxia; they were older at presentation and had intact tendon reflexes. Larger GAA expansions correlated with earlier age at onset and shorter times to loss of ambulation. The size of the GAA expansions (and particularly that of the smaller of each pair) was associated with the frequency of cardiomyopathy and loss of reflexes in the upper limbs. The GAA repeats were unstable during transmission.

CONCLUSIONS

The clinical spectrum of Friedreich's ataxia is broader than previously recognized, and the direct molecular test for the GAA expansion on chromosome 9 is useful for diagnosis, determination of prognosis, and genetic counseling.

Authors+Show Affiliations

Fédération de Neurologie and INSERM Unité 289, Hôpital de la Saltpétriere, Paris, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8815938

Citation

Dürr, A, et al. "Clinical and Genetic Abnormalities in Patients With Friedreich's Ataxia." The New England Journal of Medicine, vol. 335, no. 16, 1996, pp. 1169-75.
Dürr A, Cossee M, Agid Y, et al. Clinical and genetic abnormalities in patients with Friedreich's ataxia. N Engl J Med. 1996;335(16):1169-75.
Dürr, A., Cossee, M., Agid, Y., Campuzano, V., Mignard, C., Penet, C., Mandel, J. L., Brice, A., & Koenig, M. (1996). Clinical and genetic abnormalities in patients with Friedreich's ataxia. The New England Journal of Medicine, 335(16), 1169-75.
Dürr A, et al. Clinical and Genetic Abnormalities in Patients With Friedreich's Ataxia. N Engl J Med. 1996 Oct 17;335(16):1169-75. PubMed PMID: 8815938.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clinical and genetic abnormalities in patients with Friedreich's ataxia. AU - Dürr,A, AU - Cossee,M, AU - Agid,Y, AU - Campuzano,V, AU - Mignard,C, AU - Penet,C, AU - Mandel,J L, AU - Brice,A, AU - Koenig,M, PY - 1996/10/17/pubmed PY - 1996/10/17/medline PY - 1996/10/17/entrez SP - 1169 EP - 75 JF - The New England journal of medicine JO - N Engl J Med VL - 335 IS - 16 N2 - BACKGROUND: Friedreich's ataxia, the most common inherited ataxia, is associated with a mutation that consists of an unstable expansion of GAA repeats in the first intron of the frataxin gene on chromosome 9, which encodes a protein of unknown function. METHODS: We studied 187 patients with autosomal recessive ataxia, determined the size of the GAA expansions, and analyzed the clinical manifestations in relation to the number of GAA repeats and the duration of disease. RESULTS: One hundred forty of the 187 patients, with ages at onset ranging from 2 to 51 years, were homozygous for a GAA expansion that had 120 to 1700 repeats of the trinucleotides. About one quarter of the patients, despite being homozygous, had atypical Friedreich's ataxia; they were older at presentation and had intact tendon reflexes. Larger GAA expansions correlated with earlier age at onset and shorter times to loss of ambulation. The size of the GAA expansions (and particularly that of the smaller of each pair) was associated with the frequency of cardiomyopathy and loss of reflexes in the upper limbs. The GAA repeats were unstable during transmission. CONCLUSIONS: The clinical spectrum of Friedreich's ataxia is broader than previously recognized, and the direct molecular test for the GAA expansion on chromosome 9 is useful for diagnosis, determination of prognosis, and genetic counseling. SN - 0028-4793 UR - https://www.unboundmedicine.com/medline/citation/8815938/Clinical_and_genetic_abnormalities_in_patients_with_Friedreich's_ataxia_ L2 - https://www.nejm.org/doi/10.1056/NEJM199610173351601?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -