RESUMEN
BACKGROUND: The spinocerebellar ataxias (SCAs) are clinically heterogeneous disorders caused by triplet repeat expansions in the sequence of specific disease genes. Spinocerebellar ataxia type 8 (SCA8), originally described in a family characterized by pure cerebellar ataxia with slow disease progression, presents with expansion of combined CTA/CTG repeats. OBJECTIVE: To perform SCA8 repeat expansion analysis in a heterogeneous group of ataxic patients, to determine the prevalence of this mutation in our patients and establish the frequency of expanded CTA/CTG repeats in a large group of control subjects. PATIENTS: One hundred sixty-seven patients affected by sporadic, autosomal dominant and recessive hereditary ataxia were clinically examined and analyzed for SCA8 expansion. We further studied 161 control subjects and 125 patients with psychiatric disorders. RESULTS: We found abnormally expanded CTA/CTG repeats in 5 ataxic patients, 3 of them characterized by pure cerebellar ataxia. One patient had vitamin E deficiency and 1 patient with a sporadic case was affected by gluten ataxia. No evidence of expanded alleles was found in healthy control subjects and in patients with psychiatric disorders. CONCLUSIONS: Our data support the evidence that CTG expansions may be linked to SCA8, since the pathogenic expansions have been found only among patients with genetically unidentified forms of hereditary and sporadic ataxia. Patients carrying expanded alleles present peculiar phenotypic features, thus suggesting that unknown additional factors could probably predispose to the disease.
Asunto(s)
Proteínas del Tejido Nervioso/genética , Ataxias Espinocerebelosas/genética , Expansión de Repetición de Trinucleótido , Adulto , Anciano , Femenino , Predisposición Genética a la Enfermedad , Humanos , Italia , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , ARN Largo no Codificante , ARN no Traducido , Ataxias Espinocerebelosas/fisiopatologíaRESUMEN
BACKGROUND: The aim of this study is to analyze the segregation of the 102T/C polymorphism in the serotonin 2A receptor gene in patients affected by sporadic and familial Alzheimer's disease (FAD) with and without psychotic symptoms. METHODS: The polymorphism was analyzed in 275 subjects. A semistructured interview was used to obtain information about delusions, hallucinations, and other specific behavioral signs occurring during the disease. RESULTS: Fifty-two percent of AD patients with psychotic symptoms were homozygous for the C102 allele, as compared with 6.9% of AD patients without psychosis. Similarly, the C102/C102 genotype was significantly more frequent in FAD patients with psychosis than in FAD patients without (46.5% vs. 7.8%). CONCLUSIONS: Our data strongly confirm and extend to FAD previous studies suggesting that the genetic variation at this locus is associated with prominent psychotic features in AD and that the 102C allele could play an important role in late-onset AD.
Asunto(s)
Enfermedad de Alzheimer/genética , Polimorfismo Genético/genética , Trastornos Psicóticos/genética , Trastornos Psicóticos/metabolismo , Receptores de Serotonina/genética , Receptores de Serotonina/metabolismo , Anciano , Enfermedad de Alzheimer/psicología , Apolipoproteínas E/genética , Femenino , Amplificación de Genes , Expresión Génica/genética , Frecuencia de los Genes , Genotipo , Homocigoto , Humanos , Masculino , Mutación Puntual/genética , Trastornos Psicóticos/etiologíaRESUMEN
A 5-bp deletion and a Val1000 polymorphism at the alpha(2)-macroglobulin (A2M) gene have recently been reported to be associated with late onset Alzheimer's disease (AD). As recently it has been suggested that the effect of the A2M gene on AD susceptibility may be limited to certain populations or families, we analyzed the segregation of A2M and apolipoprotein E polymorphisms in Italian sporadic and familial AD. We analyzed the two polymorphisms in a total of 346 subjects including 98 controls by polymerase chain reaction-restriction fragment length polymorphism method. Our data do not confirm these associations, in particular we found a significant decrease of the deletion allele in AD with respect to controls. Our data do not support a role for the A2M gene as genetic risk factor for AD.
Asunto(s)
Enfermedad de Alzheimer/genética , Polimorfismo Genético/genética , alfa-Macroglobulinas/genética , Anciano , Alelos , Apolipoproteínas E/genética , Femenino , Genotipo , Humanos , Italia , Masculino , Persona de Mediana Edad , Mutación/genéticaRESUMEN
Numerous studies have provided evidence for a genetic association of the Apolipoprotein E (ApoE) epsilon4 allele and late onset familial and sporadic Alzheimer's disease (AD). Clinical observations show that a proportion of schizophrenic patients may suffer from severe cognitive impairment. That could reflect a particular clinical aspect of this mental disorder or a common, yet unknown, neurodegenerative mechanism. We analysed the ApoE gene polymorphism in a sample of 69 Italian patients with schizophrenia, 140 AD patients and 121 controls. In schizophrenic patients, the distribution of ApoE genotypes does not significantly differ from that of controls. No effect of the ApoE genotype on age of onset was found. The frequency of ApoE alleles in Italian schizophrenic patients is comparable with control values, suggesting that ApoE polymorphism does not represent a risk factor for schizophrenia.
Asunto(s)
Enfermedad de Alzheimer/genética , Apolipoproteínas E/genética , Polimorfismo Genético , Esquizofrenia/genética , Edad de Inicio , Anciano , Alelos , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Italia , Masculino , Persona de Mediana Edad , Valores de ReferenciaRESUMEN
Normal pressure hydrocephalus (NPH) is characterized by dementia, gait disorders and urinary incontinence. Apolipoprotein E (ApoE) epsilon4 allele has been associated with severity of dementia in Alzheimer's disease (AD) and in other forms of dementia. Moreover, homozygosity of the A allele of the alpha1-antichymotrypsin (ACT) gene and of allele 1 of the presenilin-1 (PS-1) gene was associated with an increased risk for late onset AD. We analyzed the distribution of ApoE, ACT and PS-1 genotypes and the corresponding allele frequencies in 13 NPH patients. No differences were found in ACT and PS-1 polymorphism distributions in the patients studied with respect to the control group. An increased ApoE epsilon4 allele frequency was observed in NPH patients with respect to controls, thus suggesting that epsilon4 allele may also be involved in the pathogenesis of the disease.
Asunto(s)
Apolipoproteínas E/genética , Demencia/genética , Hidrocéfalo Normotenso/genética , Proteínas de la Membrana/genética , alfa 1-Antiquimotripsina/genética , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Demencia/etiología , Femenino , Genotipo , Humanos , Hidrocéfalo Normotenso/complicaciones , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Presenilina-1 , PronósticoRESUMEN
A recent observation has shown that a common polymorphism in the alpha1-antichymotrypsin (ACT) gene modifies the apolipoprotein E (ApoE) epsilon4-associated Alzheimer's disease (AD) risk identifying the combination of the ACT/AA and ApoE epsilon4/epsilon4 genotypes as a potential susceptibility marker for AD. We analyzed the segregation of the ApoE and ACT polymorphism in sporadic and familial AD patients. In none of the sporadic AD patients did we find the combination of the ACT/AA and ApoE epsilon4/epsilon4 genotypes. The frequency of ApoE epsilon4/epsilon4 homozygosity in the AD sample resulted highest for the ACT/ TT genotype (17.6%). Our data fail to confirm any additional association with AD beyond the ApoE epsilon4 allele with any ACT genotype, suggesting that ACT does not represent an additional risk factor for AD.
Asunto(s)
Enfermedad de Alzheimer/genética , Apolipoproteínas E/genética , Polimorfismo Genético , alfa 1-Antiquimotripsina/genética , Adulto , Edad de Inicio , Anciano , Alelos , Genotipo , Homocigoto , Humanos , Persona de Mediana EdadRESUMEN
Our purpose was to test the dopamine D2 receptor gene (DRD2), the tyrosine hydroxylase (TH) gene and the monoamino oxydase A (MAO-A) gene for linkage to schizophrenia and bipolar disorders. We have analyzed seven Italian families with schizophrenia and four families with bipolar disorders for a total of 68 individuals; 32 individuals were affected. Diagnoses were made using the structured clinical interview Schedule for Affective Disorders and Schizophrenia, Lifetime version (SADS-L). The results of our study provide no evidence of linkage between alleles at D2 dopamine receptor loci and schizophrenia or bipolar disorders. The markers TH gene and MAO-A gene give slightly positive or negative results suggesting the utility of further analysis on more informative families.