RESUMEN
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.
Asunto(s)
Ataxia Cerebelosa/genética , Adulto , Alelos , Ataxia Cerebelosa/etnología , Femenino , Francia , Ligamiento Genético , Humanos , Masculino , Persona de Mediana Edad , Linaje , Polimorfismo GenéticoRESUMEN
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.
Asunto(s)
Degeneraciones Espinocerebelosas/genética , Adulto , Anciano , Anciano de 80 o más Años , Mapeo Cromosómico , Femenino , Ligamiento Genético , Marcadores Genéticos , Humanos , Escala de Lod , Masculino , Persona de Mediana Edad , Linaje , Reacción en Cadena de la Polimerasa , TúnezRESUMEN
Twenty five hyperthyroid patients and 25 healthy volunteers were evaluated for carbohydrate metabolic disturbance with an oral glucose tolerance test and glycosylated haemoglobin percentage. Insulin secretory response was studied in 17 hyperthyroids and 10 controls. A varying degree of abnormality was noted in hyperthyroids. Forty per cent patients had a significantly higher glycosylated haemoglobin and 3 (12%) patients had impaired glucose tolerance and 1 (4%) patient had frank diabetes mellitus. Significant hyperinsulinism was seen in the hyperthyroid group. Our data suggests that carbohydrate metabolic aberration exists in hyperthyroids and may reflect insulin resistance.
RESUMEN
Fever with rash is a common cause for dermatological referral. The causes can range from viral to protozoal, bacterial or spirochaetal. A case of rickettsial fever is reported.
RESUMEN
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.