Spinocerebellar ataxia 3 and Machado-Joseph disease: clinical, molecular, and neuropathological features.

Alexandra Durr, Giovanni Stevanin, Geraldine Cancel, Charles Duyckaerts, Nacer Abbas, Olivier Didierjean, Herve Chneiweiss, Ali Benomar, Olivier Lyon-Caen, Jean Julien, Michel Serdaru, Christiane Penet, Yves Agid, Alexis Brice
Ann Neurol.. 1996-04-01; 39(4): 490-499
DOI: 10.1002/ana.410390411

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1. Ann Neurol. 1996 Apr;39(4):490-9.

Spinocerebellar ataxia 3 and Machado-Joseph disease: clinical, molecular, and
neuropathological features.

Dürr A(1), Stevanin G, Cancel G, Duyckaerts C, Abbas N, Didierjean O, Chneiweiss
H, Benomar A, Lyon-Caen O, Julien J, Serdaru M, Penet C, Agid Y, Brice A.

Author information:
(1)INSERM U289, Hôpital de la Salpêtrière, Paris, France.

Patients with spinocerebellar ataxia 3 (SCA3) and Machado-Joseph disease (MJD)
carry an expanded CAG repeat in the MJD1 gene. One hundred twenty families of
different geographic origin with autosomal dominant cerebellar ataxia (ADCA) type
I were tested. Thirty-four families (126 patients) carried an expanded CAG
repeat. The expanded and the normal allele did not overlap and the repeat was
unstable during transmission, with variation in the size of the CAG length
ranging from -8 to +5 and a mean expansion of 0.86 repeats without differences
according to the parental sex. There was a combined effect of the number of CAG
repeats of the expanded and normal allele on the age at onset, which accounted
for 70% of its variability. The length of the CAG repeat influenced the frequency
of clinical signs associated with cerebellar ataxia, such as abnormal tendon
reflexes or decreased vibration sense, whereas the interindividual variation of
supranuclear ophthalmoplegia, sphincter and swallowing difficulties, and
amyotrophy was mostly determined by different disease durations. We compared the
clinical profile of 91 SCA3/MJD patients with 51 SCA1 and 32 SCA2 patients. There
were striking differences between the SCA3/MJD and SCA2 but not with SCA1 groups
of patients. Despite their clinical similarities, distinct neuropathological
features were observed in 2 SCA3/MJD and 2 SCA1 patients.

DOI: 10.1002/ana.410390411
PMID: 8619527 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus