PubMed Health⌕ Search

Biomedical subjects

G Stevanin

Publications and source records attributed to G Stevanin.

65 records · Page 4Linked to original sources
PubMed1994

The gene for Machado-Joseph disease maps to the same 3-cM interval as the spinal cerebellar ataxia 3 gene on chromosome 14q.

Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder in families of Portuguese-Azorean ancestry. The gene responsible for MJD has been assigned to a 29-cM interval on chromosome 14q. A large Brazilian family with MJD was genotyped with six new microsatellite markers spanning 19 cM on chromosome 14q. Linkage analysis and haplotype reconstruction reduced the MJD candidate region to a 3-cM interval between markers D14S280 and D14S81, permitting positional cloning. This interval also contains the spinal cerebellar ataxia 3 (SCA3) gene, responsible for a genetic subtype of the type I autosomal dominant cerebellar ataxias, clinically related to MJD. This result supports the hypothesis that abnormalities in the same gene may be responsible for both disorders. The minor clinical differences between the two diseases may result from allelic heterogeneity.

Cerebellar Ataxia↗
PubMed1994

Clinical and genetic analysis of a Tunisian family with autosomal dominant cerebellar ataxia type 1 linked to the SCA2 locus.

Autosomal dominant cerebellar ataxias (ADCA) type 1 are a clinically and genetically heterogeneous group of neurodegenerative disorders. We report a large Tunisian ADCA type 1 family in which 17 patients (mean age at onset +/- SD = 35.6 +/- 15.3 years) were examined. There was mean anticipation of 10.3 +/- 15.4 years in this family; anticipation was greater in paternal (28 +/- 8.2 years) than in maternal (2.7 +/- 10.9 years) transmission. Linkage analysis performed with microsatellite markers linked to the spinal cerebellar ataxia 1 (SCA1) locus on chromosome 6p and the SCA2 locus on chromosome 12q excluded linkage to SCA1, but there was close linkage with marker D12S105 (Zmax = 2.51 at theta = 0.00). This result was confirmed by multipoint analysis, which generated a maximal lod score of 3.46 at this locus. Multipoint analysis and haplotype reconstruction reduced the interval containing the SCA2 locus to 6.4 cM, a narrowing of the 35-cM interval in a previously described Cuban SCA2 family with a clinical picture similar to that of our family, including a high frequency of postural and action tremor.

Adult↗
PubMed1994

A third locus for autosomal dominant cerebellar ataxia type I maps to chromosome 14q24.3-qter: evidence for the existence of a fourth locus.

The autosomal dominant cerebellar ataxias (ADCA) type I are a group of neurological disorders that are clinically and genetically heterogeneous. Two genes implicated in the disease, SCA1 (spinal cerebellar ataxia 1) and SCA2, are already localized. We have mapped a third locus to chromosome 14q24.3-qter, by linkage analysis in a non-SCA1/non-SCA2 family and have confirmed its existence in a second such family. We suggest designating this new locus "SCA3". Combined analysis of the two families restricted the SCA3 locus to a 15-cM interval between markers D14S67 and D14S81. The gene for Machado-Joseph disease (MJD), a clinically different form of ADCA type I, has been recently assigned to chromosome 14q24.3-q32. Although the SCA3 locus is within the MJD region, linkage analyses cannot yet demonstrate whether they result from mutations of the same gene. Linkage to all three loci (SCA1, SCA2, and SCA3) was excluded in another family, which indicates the existence of a fourth ADCA type I locus.

Adult↗
PubMed1993

Phenotypic variability in autosomal dominant cerebellar ataxia type I is unrelated to genetic heterogeneity.

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.

Adolescent↗
PubMed1993

Familial essential tremor and idiopathic torsion dystonia are different genetic entities.

Familial essential tremor (ET) is an autosomal dominant disorder presenting as an isolated postural tremor. Its frequent association with dystonia suggests that the two disorders might be pathogenically related. We report the exclusion of the DYT1 locus on chromosome 9q32-34, responsible for idiopathic torsion dystonia (ITD), in two large ET families. We conclude that ET and ITD are distinct genetic disorders.

Adolescent↗
PubMed1993

Genetic heterogeneity of autosomal dominant cerebellar ataxia type 1: clinical and genetic analysis of 10 French families.

We performed linkage analysis between the gene responsible for spinal cerebellar ataxia 1 (SCA1) and the highly polymorphic chromosome 6 locus, D6S89, in 10 French families with autosomal dominant cerebellar ataxia (ADCA) type 1. These families were clinically indistinguishable except for one family with loss of hearing and vision. Very close linkage was observed in four families, with no evidence of recombination between SCA1 and D6S89. Linkage with D6S89 was excluded in the six others, thus demonstrating genetic heterogeneity for ADCA type 1. The D6S89 marker, which is very closely linked to the disease locus, can be used to identify SCA1 families and will lead to predictive testing.

Adult↗
PubMed1992

Duplication within chromosome 17p11.2 in 12 families of French ancestry with Charcot-Marie-Tooth disease type 1a. The French CMT Research Group.

Hereditary motor and sensory neuropathy type I (HMSN I), also designated Charcot-Marie-Tooth disease type 1 (CMT1), is a peripheral neuropathy frequently inherited as an autosomal dominant trait, characterised by progressive distal muscular atrophy and sensory loss with markedly decreased nerve conduction velocity. A duplication within chromosome 17p11.2, cosegregating with the disease, has recently been reported in several CMT1a families. In order to estimate the frequency of this anomaly and determine the location of a duplication in this region, 12 CMT1 families were analysed with polymorphic DNA markers located within 17p11.2-12. Duplications were found in all families including loci D17S61 (EW401), D17S122 (VAW409R3a and RM11-GT), and D17S125 (VAW412R3). The duplications were completely linked and associated with the disease (lod score of 20.77 at zero recombination). Screening for the RM11-GT microsatellite showed that most of the duplicated haplotypes were heterozygous, supporting the hypothesis that the duplication resulted from an unequal crossing over. There was no significant haplotype association within the duplicated region suggesting that the duplication resulted de novo as an independent event in each family. In one family, recombination within the duplicated region was observed, indicating that genetic instability in 17p11.2 might be related to a high recombination rate. Since most cases of CMT1a seem to result from this segmental trisomy, it can be used as a basis for DNA diagnosis of the disease.

Base Sequence↗