Phenotypic variability in autosomal dominant cerebellar ataxia type I is unrelated to genetic heterogeneity.
Brain. 1993-12-01; 116(6): 1497-1508
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1. Brain. 1993 Dec;116 ( Pt 6):1497-508.
Phenotypic variability in autosomal dominant cerebellar ataxia type I is
unrelated to genetic heterogeneity.
Dürr A(1), Chneiweiss H, Khati C, Stevanin G, Cancel G, Feingold J, Agid Y, Brice
(1)INSERM U 289, Hôpital de la Salpêtrière, Paris, France.
Families with autosomal dominant cerebellar ataxia (ADCA), a heterogeneous group
of diseases, were investigated prior to and during genetic linkage analysis. We
report here on the clinical features of 122 affected individuals from 36
unrelated families with ADCA type I, the most common type. Our results indicate
an anticipation expressed in a mean 9.4 year earlier age at onset and more rapid
clinical progression in successive generations. There was no imprinting, since
age at onset, disease duration and severity of the disease were independent of
parental transmission. Progressive cerebellar ataxia was variably associated with
signs such as ophthalmoplegia, dysphagia, sphincter disturbances, briskness or
loss of tendon reflexes, decreased vibration sense and amyotrophy, a variability
correlated with disease duration. Linkage analysis of 10 informative families
with microsatellite markers, located on the short arm of the chromosome 6,
allowed the identification of four families showing positive linkage to the SCA1
(spinal cerebellar ataxia 1) locus and six non-SCA1 families for whom linkage to
this locus was excluded. This reflects non-allelic genetic heterogeneity. Thus,
the analysis of clinical signs associated with cerebellar ataxia in SCA1 versus
non-SCA1 kindreds did not distinguish between the two groups. The clinical
picture of ADCA type I did not reflect the genetic heterogeneity of the disease.
PMID: 8293283 [Indexed for MEDLINE]