ABSTRACT
BACKGROUND: Between January 1993 and December 2003, 19 patients with familial prion diseases due to the D178N mutation were referred to the regional epidemiological registry for spongiform encephalopathies in the Basque Country in Spain, a small community of some 2,100,000 inhabitants. METHODS: Ten further patients belonging to the same pedigrees were retrospectively ascertained through neurological or neuropathological records. In four of the patients, the diagnosis was confirmed by analysing DNA obtained from paraffin blocks. In this article, we report on the clinical, genetic, and pathological features of the 23 patients carrying the D178N mutation confirmed by genetic molecular analysis. Haplotyping studies suggest a founder effect among Basque born families, explaining in part this unusually high incidence of the D178N mutation in a small community. Only two patients (8%) lack familial antecedents. RESULTS: We have observed a phenotypic variability even among homozygous 129MM patients. Our findings challenge the currently accepted belief that MM homozygosity in codon 129 is always related to a fatal familial insomnia (FFI) phenotype. Indeed, seven out of 17 patients with a 129MM genotype in this series presented with a Creutzfeldt-Jakob disease (CJD) clinicopathological picture. CONCLUSIONS: The considerable clinical and pathological overlapping observed among homozygous 129MM patients favours the view that FFI and CJD178 are the extremes of a spectrum rather than two discrete and separate entities. Other genetic or environmental factors apart from the polymorphism in codon 129 may play a role in determining the phenotypic expression of the D178N mutation in the PRNP gene.
Subject(s)
Amyloid/genetics , Creutzfeldt-Jakob Syndrome/genetics , Genetic Variation/genetics , Phenotype , Point Mutation/genetics , Adult , Age of Onset , Aged , Codon , Creutzfeldt-Jakob Syndrome/ethnology , DNA Mutational Analysis , Female , Founder Effect , Haplotypes , Humans , Incidence , Male , Middle Aged , PrPSc Proteins/genetics , Prospective Studies , Sleep Initiation and Maintenance Disorders/epidemiology , SpainABSTRACT
Previous studies have suggested that mitochondrial metabolism and/or mitochondrial DNA (mtDNA) could be, in conjunction with other genetic or environmental factors, a risk factor for the development of multiple sclerosis (MS). One of these studies establishes that mitochondrial haplogroup JT is a risk factor for developing the disease, in particular the visual manifestations [optic neuritis (ON)]. Nevertheless, as distribution of these haplogroups varies between populations, the observed association may be due to a slanted sample with no physiopathological value. This hypothesis was checked with MS patients, originals from Basque country (this population has peculiar genetic characteristics) and from other Spanish regions. We concluded that such an association does not exist. By contrast, a decrease could be seen in the frequency of the JT haplogroup in the ON group and in the MS-Basque group. That trend could be a protective effect, which needs to be verified in further investigations.
Subject(s)
DNA, Mitochondrial/genetics , Multiple Sclerosis/epidemiology , Multiple Sclerosis/genetics , Adult , Aged , Female , Genetic Predisposition to Disease/epidemiology , Haplotypes , Humans , Male , Middle Aged , Optic Neuritis/epidemiology , Optic Neuritis/genetics , Point Mutation , Risk Factors , Spain/epidemiologySubject(s)
Demyelinating Diseases/complications , Immunoglobulin G/immunology , Polyneuropathies/complications , Aged , Demyelinating Diseases/immunology , Demyelinating Diseases/physiopathology , Evoked Potentials, Somatosensory/physiology , Gangliosidosis, GM1/immunology , Humans , Immunoglobulin M/immunology , Male , Muscle Weakness/physiopathology , Muscle, Skeletal/physiopathology , Polyneuropathies/immunology , Polyneuropathies/physiopathology , SyndromeABSTRACT
No disponible
Subject(s)
Middle Aged , Adult , Aged, 80 and over , Aged , Male , Female , Humans , Paraparesis, Tropical Spastic , Health Care Costs , Myotonic Dystrophy , Myasthenia Gravis , Cerebral Infarction , Acute Disease , Hospitalization , TelencephalonABSTRACT
No disponible
No disponible
Subject(s)
Aged , Male , Humans , Syndrome , Gangliosidosis, GM1 , Muscle, Skeletal , Muscle Weakness , Polyneuropathies , Demyelinating Diseases , Immunoglobulin G , Immunoglobulin M , Evoked Potentials, SomatosensoryABSTRACT
Trigeminal sensory involvement was noted in 14 out of 24 cases of Bell's palsy. The authors describe its characteristics and its chronology with regard to the facial paralysis. Then they propose a vascular mechanism for this association on the basis of two kinds of data. First it is known that there is a common arterial supply of the VIIth and Vth cranial nerves through the middle meningeal vascular system. Secondly some exceptional complications of embolisation within that system have included involvement of both VIIth and Vth sensory nerves. These facts support the vascular basis of Bell's palsy and present an example of a vascular territorial pathology in cranial nerve involvement.
