Correlation between left ventricular hypertrophy and GAA trinucleotide repeat length in Friedreich's ataxia.

Abstract:

BACKGROUND:Friedreich's ataxia (FA), the most common inherited ataxia, is associated frequently with cardiac hypertrophy, and death is often cardiac related. Recently, the disease has been associated with a mutation that consists of an unstable expansion of GAA repeats in the first intron of the gene encoding frataxin on chromosome 9. METHODS AND RESULTS:We studied 44 consecutive patients with FA, determined the size of GAA expansions in the frataxin gene, and examined the relation between the genotype and cardiac phenotype assessed by M-mode and two-dimensional echocardiography. All the patients were homozygous for the mutation. The size of the GAA expansion on the smaller allele varied from 270 to 1200. We found a correlation between the size of GAA expansion and the left ventricular wall thickness (r = .51, P < .001) and the left ventricular mass index (r = .45, P = .002). Left ventricular hypertrophy was observed in 81% of patients with a number of GAA repeats above the median value of 770 compared with only 14% in the other group (P = .002). CONCLUSIONS:These data demonstrate that in FA, the severity of left ventricular hypertrophy is related to the number of GAA repeats. These results suggest that abnormalities of the gene encoding frataxin, a protein of unknown function highly expressed in the normal heart, may play an important role in the modulation of cardiac hypertrophy.

journal_name

Circulation

journal_title

Circulation

authors

Isnard R,Kalotka H,Dürr A,Cossée M,Schmitt M,Pousset F,Thomas D,Brice A,Koenig M,Komajda M

doi

10.1161/01.cir.95.9.2247

subject

Has Abstract

pub_date

1997-05-06 00:00:00

pages

2247-9

issue

9

eissn

0009-7322

issn

1524-4539

journal_volume

95

pub_type

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