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1.
Neuropathology ; 29(3): 280-4, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18627480

RESUMEN

Fragile X tremor/ataxia syndrome (FXTAS) occurs in individuals with moderate CGG expansion of the fragile X mental retardation 1 (FMR1) gene and is associated with intranuclear inclusions in neurons and astrocytes. Although the neuropathologic findings in the brain and spinal cord were described, pathological features in the peripheral nervous system were not reported. Here, we report on novel neuropathological findings in the peripheral nervous system and especially in autonomic ganglia at autopsy in a man with FXTAS. In addition to the characteristic brain and spinal cord findings, typical intranuclear inclusions were identified in the ganglion cells of adrenal medulla, dorsal root ganglia, paraspinal sympathetic ganglia, myenteric ganglia of the stomach and subepicardial autonomic ganglion of the heart. Our findings indicate that FXTAS diffusely involves the central and peripheral nervous systems, which explains the protean neurological symptoms ranging from dementia to dysautonomia.


Asunto(s)
Ataxia/patología , Síndrome del Cromosoma X Frágil/patología , Sistema Nervioso Periférico/patología , Anciano , Astrocitos/patología , Astrocitos/ultraestructura , Encéfalo/patología , Ganglios Autónomos/patología , Ganglios Autónomos/ultraestructura , Humanos , Masculino , Vaina de Mielina/patología , Vaina de Mielina/ultraestructura , Neuronas/patología , Neuronas/ultraestructura , Sistema Nervioso Periférico/ultraestructura , Médula Espinal/patología
2.
Hum Genet ; 124(1): 95-9, 2008 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-18587682

RESUMEN

Genetic variants in embryonic lethal, abnormal vision, Drosophila-like 4 (ELAVL4) have been reported to be associated with onset age of Parkinson disease (PD) or risk for PD affection in Caucasian populations. In the current study we genotyped three single nucleotide polymorphisms in ELAVL4 in a Caucasian study sample consisting of 712 PD patients and 312 unrelated controls from the GenePD study. The minor allele of rs967582 was associated with increased risk of PD (odds ratio = 1.46, nominal P value = 0.011) in the GenePD population. The minor allele of rs967582 was also the risk allele for PD affection or earlier onset age in the previously studied populations. This replication of association with rs967582 in a third cohort further implicates ELAVL4 as a PD susceptibility gene.


Asunto(s)
Proteínas ELAV/genética , Ligamiento Genético , Enfermedad de Parkinson/genética , Edad de Inicio , Anciano , Estudios de Cohortes , Bases de Datos Genéticas , Proteínas ELAV/fisiología , Proteína 4 Similar a ELAV , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Humanos , Masculino , Metaanálisis como Asunto , Persona de Mediana Edad , Polimorfismo Genético
3.
BMC Med ; 6: 32, 2008 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-18986508

RESUMEN

BACKGROUND: We report age-dependent penetrance estimates for leucine-rich repeat kinase 2 (LRRK2)-related Parkinson's disease (PD) in a large sample of familial PD. The most frequently seen LRRK2 mutation, Gly2019Ser (G2019S), is associated with approximately 5 to 6% of familial PD cases and 1 to 2% of idiopathic cases, making it the most common known genetic cause of PD. Studies of the penetrance of LRRK2 mutations have produced a wide range of estimates, possibly due to differences in study design and recruitment, including in particular differences between samples of familial PD versus sporadic PD. METHODS: A sample, including 903 affected and 58 unaffected members from 509 families ascertained for having two or more PD-affected members, 126 randomly ascertained PD patients and 197 controls, was screened for five different LRRK2 mutations. Penetrance was estimated in families of LRRK2 carriers with consideration of the inherent bias towards increased penetrance in a familial sample. RESULTS: Thirty-one out of 509 families with multiple cases of PD (6.1%) were found to have 58 LRRK2 mutation carriers (6.4%). Twenty-nine of the 31 families had G2019S mutations while two had R1441C mutations. No mutations were identified among controls or unaffected relatives of PD cases. Nine PD-affected relatives of G2019S carriers did not carry the LRRK2 mutation themselves. At the maximum observed age range of 90 to 94 years, the unbiased estimated penetrance was 67% for G2019S families, compared with a baseline PD risk of 17% seen in the non-LRRK2-related PD families. CONCLUSION: Lifetime penetrance of LRRK2 estimated in the unascertained relatives of multiplex PD families is greater than that reported in studies of sporadically ascertained LRRK2 cases, suggesting that inherited susceptibility factors may modify the penetrance of LRRK2 mutations. In addition, the presence of nine PD phenocopies in the LRRK2 families suggests that these susceptibility factors may also increase the risk of non-LRRK2-related PD. No differences in penetrance were found between men and women, suggesting that the factors that influence penetrance for LRRK2 carriers are independent of the factors which increase PD prevalence in men.


Asunto(s)
Glicina/genética , Mutación/genética , Enfermedad de Parkinson/genética , Penetrancia , Proteínas Serina-Treonina Quinasas/genética , Serina/genética , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/patología , Distribución Aleatoria , Factores Sexuales
4.
Mov Disord ; 23(11): 1596-601, 2008 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-18649400

RESUMEN

The ATP/ADP ratio reflects mitochondrial function and has been reported to be influenced by the size of the Huntington disease gene (HD) repeat. Impaired mitochondrial function has long been implicated in the pathogenesis of Parkinson's disease (PD), and therefore, we evaluated the relationship of the HD CAG repeat size to PD onset age in a large sample of familial PD cases. PD affected siblings (n = 495), with known onset ages from 248 families, were genotyped for the HD CAG repeat. Genotyping failed in 11 cases leaving 484 for analysis, including 35 LRRK2 carriers. All cases had HD CAG repeats (range, 15-34) below the clinical range for HD, although 5.2% of the sample (n = 25) had repeats in the intermediate range (the intermediate range lower limit = 27; upper limit = 35 repeats), suggesting that the prevalence of intermediate allele carriers in the general population is significant. No relation between the HD CAG repeat size and the age at onset for PD was found in this sample of familial PD.


Asunto(s)
Salud de la Familia , Enfermedad de Huntington/genética , Proteínas del Tejido Nervioso/genética , Proteínas Nucleares/genética , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/fisiopatología , Repeticiones de Trinucleótidos/genética , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Femenino , Genotipo , Humanos , Proteína Huntingtina , Enfermedad de Huntington/epidemiología , Masculino , Persona de Mediana Edad
5.
Neurol Clin Pract ; 3(1): 4-7, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29406522

RESUMEN

The relationship between head trauma and parkinsonism has been debated since James Parkinson's first description of the shaking palsy in the late 19th century. We observed in our outpatient clinic a young woman in whom hemiparkinsonism developed within 3 weeks of sustaining closed head trauma with loss of consciousness. The patient had a discrete unilateral midbrain hemorrhage on head MRI which involved the contralateral substantia nigra. The condition responded well to carbidopa/levodopa. This patient is a convincing example of posttraumatic midbrain hemorrhage causing parkinsonism.

6.
Alzheimer Dis Assoc Disord ; 21(3): 262-4, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17804960

RESUMEN

Few women with Fragile X tremor ataxia syndrome (FXTAS) have been reported. They have milder manifestations at a later age than men. This gender difference may be related to the X inactivation pattern in women. We describe a woman who presented to her geriatrician with poor memory and was found to have ataxia and tremor. Additional queries yielded history of premature ovarian failure. Genetic testing showed heterozygous fragile X mental retardation gene premutation with 103 CGG repeats in the abnormal allele and 31 CGG repeats in the normal allele. Also, the X inactivation pattern was skewed with the active X chromosome predominantly having the premutation allele. We believe that FXTAS is more common in women than is generally thought and that many such patients masquerade as dementia of old age. Action tremor and ataxia associated with a history suggestive of premature ovarian failure should raise suspicions for FXTAS.


Asunto(s)
Enfermedad de Alzheimer/diagnóstico , Cromosomas Humanos X/genética , Síndrome del Cromosoma X Frágil/diagnóstico , Mutación/genética , Insuficiencia Ovárica Primaria/genética , Anciano , Diagnóstico Diferencial , Femenino , Síndrome del Cromosoma X Frágil/complicaciones , Síndrome del Cromosoma X Frágil/genética , Humanos
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