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Biomedical subjects

A López de Munain

Publications and source records attributed to A López de Munain.

At least 19 recordsLinked to original sources
PubMed2006

Genes related to iron metabolism and susceptibility to Alzheimer's disease in Basque population.

Alzheimer's disease (AD) is the most common dementing disorder and presents with a progressive and irreversible cognitive decline of gradual onset. To date, several reports have involved iron in AD physiopathology. In this study, we have analysed TFC2 variant and HFE mutations (H63D and C282Y) in 211 AD patients and 167 controls recruited from an area of the Basque Country. Furthermore, we have studied APOE genotype as it is a well-known risk factor for AD. APOE epsilon 4 allele was associated with an increased risk of AD and an earlier age at onset, whereas no association was found between TFC2 or HFE C282Y mutation and disease susceptibility. The frequency of H63D mutation was higher in control population (29.9%) than in AD patients (18%), suggesting a protective role of this allele on AD either due to the presence of the mutation itself or through the effect of other related genes in the ancestral haplotype in which it is included.

Aged↗
PubMed2006

Apolipoprotein E epsilon4 allele in familial and sporadic Parkinson's disease.

Parkinson's disease (PD) is the second most common age-related neurodegenerative disease after Alzheimer's disease (AD). Common risk factors for both diseases have been explored to study potential etiologic interactions between these two neurodegenerative disorders. The APOE epsilon4 allele, previously associated with AD, has also been associated with risk of PD and with the presence of some clinical features in PD patients. However, the role of APOE epsilon4 allele in risk of PD remains unclear. We studied the distribution of APOE alleles in 276 unrelated familial and sporadic PD patients and in 212 controls. Patients and controls were classified by ethnicity. No genetic heterogeneity between Basques and people from other regions of Spain was found. No significant differences in APOE allele distribution between PD patients and controls were found; however, lower epsilon4 allele frequency was observed when the sporadic PD group was analyzed separately. By contrast, an increase in epsilon4 allele frequency was found in familial PD patients with cognitive decline. We conclude that the APOE epsilon4 allele may be associated with the risk of developing PD in isolated cases and that it is linked to the presence of cognitive decline in familial PD in our sample.

Age of Onset↗
PubMed2006

Genetic analysis of the LGI/Epitempin gene family in sporadic and familial lateral temporal lobe epilepsy.

Mutations in the LGI1/Epitempin gene cause autosomal dominant lateral temporal lobe epilepsy (ADLTE), a partial epilepsy characterized by the presence of auditory seizures. However, not all the pedigrees with a phenotype consistent with ADLTE show mutations in LGI1/Epitempin, or evidence for linkage to the 10q24 locus. Other authors as well as ourselves have found an internal repeat (EPTP, pfam# PF03736) that allowed the identification of three other genes sharing a sequence and structural similarity with LGI1/Epitempin. In this work, we present the sequencing of these genes in a set of ADLTE families without mutations in both LGI1/Epitempin and sporadic cases. No analyzed polymorphisms modified susceptibility in either the familial or sporadic forms of this partial epilepsy.

Alleles↗
PubMed2006

CD24 V/V is an allele associated with the risk of developing multiple sclerosis in the Spanish population.

The allele C in the CD24 gene has been related to multiple sclerosis (MS). In this work we check this single nucleotide polymorphism (SNP) in a population of 135 patients and 285 controls. Our results confirm the association between the V/V genotype at aa 57 of this gene and MS and highlight the importance of taking into account the origin of the subjects to avoid a population bias.

Adult↗
PubMed2005

LGMD2A: genotype-phenotype correlations based on a large mutational survey on the calpain 3 gene.

We present here the clinical, molecular and biochemical findings from 238 limb-girdle muscular dystrophy type 2A (LGMD2A) patients, representing approximately 50% (238 out of 484) of the suspected calpainopathy cases referred for the molecular study of the calpain 3 (CAPN3) gene. The mean age at onset of LGMD2A patients was approximately 14 years, and the first symptoms occurred between 6 and 18 years of age in 71% of patients. The mean age at which the patients became wheelchair bound was 32.2 years, with 84% requiring the use of a wheelchair between the age of 21 and 40 years. There was no correlation between the age at onset and the time at which the patient became wheelchair bound, nor between the sex of the patient and the risk of becoming wheelchair bound. Of the cases where the CAPN3 gene was not affected, approximately 20% were diagnosed as LGMD2I muscular dystrophy, while facioscapulohumeral muscular dystrophy (FSHD) was uncommon in this sample. We identified 105 different mutations in the CAPN3 gene of which 50 have not been described previously. These were distributed throughout the coding region of the gene, although some exons remained free of mutations. The most frequent mutation was 2362AG-->TCATCT (exon 22), which was present in 30.7% of the chromosomes analysed (146 chromosomes). Other recurrent mutations described were N50S, 550DeltaA, G222R, IVS6-1G-->A, A483D, IVS17+1G-->T, 2069-2070DeltaAC, R748Q and R748X, each of which was found in >5 chromosomes. The type of mutation in the CAPN3 gene does not appear to be a risk factor for becoming dependent on a wheelchair at a determined age. However, in the cases with two null mutations, there were significantly fewer patients that were able to walk than in the group of patients with at least one missense mutation. Despite the fact that the results of phenotyping and western blot might be biased due to multiple referral centres, producing a diagnosis on the basis of the classical phenotype is neither sufficiently sensitive (86.7%) nor specific (69.3%), although western blot proved to be even less sensitive (52.5%) yet more specific (87.8%). In this case LGMD2I was a relevant cause of false-positive diagnoses. Considering both the clinical phenotype and the biochemical information together, the probability of correctly diagnosing a calpainopathy is very high (90.8%). However, if one of the analyses is lacking, the probability varies from 78.3 to 73.7% depending on the information available. When both tests are negative, the probability that the sample comes from a patient with LGMD2A was 12.2%.

Adolescent↗
PubMed2005

Phenotypic variability in familial prion diseases due to the D178N mutation.

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.

Adult↗
PubMed2005

[Analysis of gait and movement of upper limbs in muscular dystrophies].

INTRODUCTION: The objective is to analyze gait and upper extremity movement in a sample of healthy individuals and patients with different muscular dystrophies and to determine the relationship of the obtained variables with the pattern of muscular involvement. SUBJECTS AND METHODS: Gait and upper limb movement was analyzed with a three-dimensional photogrammetry system. Convenience sample of 28 healthy volunteers, 40 patients with myotonic dystrophy (MD), 9 patients with facioscapulohumeral dystrophy (FSHD) and 14 patients with limb-girdle muscular dystrophy type 2A (LGMD2A). Spatio-temporal and kinematic variables were analyzed. RESULTS: Patients had lower velocity, cadence and shorter stride duration than healthy subjects. Gait and upper extremity kinematic variables suggested proximal muscular involvement in LGMD2A patients and distal muscular abnormalities in MD patients. The most characteristic finding in FSHD patients was related with dorsiflexor muscles' weakness. Some of the variables were also correlated to the patients' functional stage. CONCLUSIONS: This analysis allows the distinction of kinematic and spatio-temporal patterns of gait and upper extremity movement that correlate with muscular dystrophy's phenotype. The use of this analysis in the clinical setting to assess disease progression or the potential effects of treatments requires further studies.

Adult↗
PubMed2004

Mitochondrial polymporphisms in Parkinson's Disease.

The mtDNA polymorphisms A4336G, A10398G and T4216C have been associated with PD. While A4336G is thought to be a genetic risk factor, A10398G appears to be a protective factor and T4216C is only weakly associated with the disease. In this work we analyzed the association between these three genetic polymorphisms and PD in a Spanish-PD population. The samples were classified by ethnic origin in Basques or other origin. Our analysis confirm the association between A4336G and PD. Our results with A10398G polymorphism highlight the importance of performing the association studies in ethnically homogeneous populations.

Aged↗
PubMed2004

Prevalence of Parkinson's disease and other types of Parkinsonism. A door-to-door survey in Bidasoa, Spain.

OBJECTIVES: To assess the prevalence of Parkinson's disease and parkinsonism in two Spanish populations (Irun and Hondarribia, Bidasoa Region) and to compare the results with those of similar surveys. METHODS: The survey included 2000 participants aged 65 years or older in a door-to-door, three-phase design. In the screening phase we used the SNES (Sicilian Neuro-Epidemiologic Study) screening questionnaire, which has 100% sensitivity. In phases 2 and 3 we carried out a 3-year follow-up of all cases diagnosed with parkinsonism in phase 2. Progressively stricter diagnostic criteria were chosen in order to minimize the impact of false positives on the final results. RESULTS: The prevalence of Parkinson's disease (PD) was 1.5 % (95% confidence interval, 0.9 to 2.3) and the prevalence of other types of parkinsonism (OP) was 1.1 % (95% confidence interval 0.6 to 1.9). The overall prevalence by age group was 0.4 % (65-74 years), 4.7% (75-84 years), and 2.9% (> or =85 years) for Parkinson's disease and 0.7%, 2%, and 3.9 % for parkinsonism, respectively. The other parkinsonism prevalence was 1.3 % in men and 1.6 % in women. CONCLUSIONS: These prevalence rates are similar than those found in studies made in other European countries. The prevalence of both Parkinson's disease and other types of parkinsonism increased with age, with no significant differences between men and women.

Age Factors↗
PubMed2004

Mitochondrial haplogroups in Basque multiple sclerosis patients.

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.

Adult↗
PubMed2000

[Sleep apnea syndrome and cerebral infarction].

OBJECTIVES: To analyze the relationship between snoring and sleep apnea with brain infarction. METHODS: We studied 79 consecutive patients of both sexes with cerebral infarction and 248 age and sex matched controls. We obtained data reflecting arterial hypertension, diabetes mellitus, hypercholesterolemia, smoking and drinking habits, coronary heart disease, cardiopathy, snoring, respiratory pauses during sleep and daytime sleepiness, by using a standard questionnaire to interview every subject and his/her spouse. RESULTS: 53% of patients and 46% of controls snored often or always (p = 0.27). Snoring was significantly more frequent in men. Thirty four percent of patients and 27% of controls were snorers and suffered apnea during sleep (p = 0.19). Nineteen per cent of patients and 11% of controls presented snoring, respiratory pauses during sleep and daytime sleepiness simultaneously, suggesting obstructive sleep apnea syndrome (OSAS) (p = 0.06). However, by separately analyzing people younger than 65 years, the frequency of OSAS was significantly higher in patients (29%) than in controls (7%) (p = 0.006). Finally, 10% of patients and 3% of controls presented snoring, respiratory pauses during sleep and moderate or severe daytime sleepiness simultaneously, suggesting moderate-severe OSAS (p = 0.01). A multiple logistic regression analysis confirmed the independent contribution of moderate-severe OSAS as a risk factor for ischemic stroke, with an adjusted odds ratio of 4.54. In people younger than 65 years, OSAS, regardless of its severity, was also an independent risk factor for ischemic stroke, with an adjusted odds ratio of 5.78. CONCLUSIONS: Clinically diagnosed obstructive sleep apnea syndrome is an independent risk factor for ischemic stroke, especially in people younger than 65 years.

Adult↗
PubMed2000

[Andersen syndrome. Description of a case] .

A 17 year-old man, with periodic muscular weakness since the age of 6 years, is presented. The episodes of periodic paralysis were of variable duration, from 1 to 3 days, and were induced by physical exercise or by stress. Weakness was generalised, although predominant in anterior compartment of the legs, with foot drop. Interictal neurological examination was absolutely normal. He showed dysmorphic features, with micrognatia. Cardiac examination revealed continuous arrhythmia. Basal EKG and 24 hours EKG-Holter confirmed the existence of abundant ventricular extrasystoles, with episodes of ventricular tachycardia, without clinical manifestations. Echocardiogram was normal. Ictal and interictal ENG-EMG, and muscle and nerve biopsies were normal. Serum potassium levels during the episodes ranged from 3 to 3.6 mEq/l (N: 3.5-4.5 mEq/l), being normal interictally (4-5 mEq/l). Oral administration of potassium did not prevent the development of episodic weakness. He had no familial history of similar symptoms. This association of periodic paralysis, cardiac arrhythmia and dysmorphic features correspond to a rare entity named Andersen's syndrome.

Abnormalities, Multiple↗
PubMed1999

Autosomal dominant nocturnal frontal lobe epilepsy in a Spanish family with a Ser252Phe mutation in the CHRNA4 gene.

BACKGROUND: A large family with autosomal dominant nocturnal frontal lobe epilepsy from the south of Spain was studied. The clinical appearance of the disease in this family, which included 28 members, of whom 11 were affected and 2 were obligate carriers, was identical to that previously described in an Australian family and a Norwegian family, in which mutations in exon 5 of the CHRNA4 gene were found. METHODS: Following DNA extraction, the family was genotyped with 4 fluorescent markers flanking the locus to the CHRNA4 gene on chromosome 20q13.3, and lod score computations were performed. The exon 5 of the CHRNA4 gene was amplified between nucleotides 535 and 825 and polymerase chain reaction products were purified and sequenced directly. RESULTS: The same missense mutation as that found in the Australian family, C-->T, which causes the replacement of a serine with phenylalanine in amino acid 252 in exon 5, was detected. This mutation segregated with the disorder in all 11 affected members, in the 2 obligate carriers, and in 1 asymptomatic sibling, and was not found in 1 spouse and 1 daughter. Neither of the 2 polymorphisms found in a series of families with epilepsy were found in our sample [corrected]. CONCLUSIONS: These data confirm the clinical homogeneity in the phenotypic expression of autosomal dominant nocturnal frontal lobe epilepsy caused by mutation in the CHRNA4 gene, and the pathogenic role of the Ser252Phe mutation in this disorder.

Adult↗
PubMed1999

Autosomal dominant lateral temporal epilepsy: clinical and genetic study of a large Basque pedigree linked to chromosome 10q.

We report a large family with a temporal partial epilepsy syndrome inherited in an autosomal dominant mode, with a penetrance of about 80%. This epilepsy syndrome is benign, with age of onset in the second or third decade of life. It is characterized by rare partial seizures, usually secondarily generalized, arising mostly during sleep, without postictal confusion. There is a good response to the antiepileptic therapy but often a recurrence of seizures after drug withdrawal. The partial component, visual (lights, colors, and simple figures) or auditory (buzzing or "humming like a machine"), the existence of temporo-occipital interictal electroencephalographic epileptiform abnormalities, and the hypoperfusion in the temporal lobe detected by interictal hexamethylpropyleneamine oxime-technetium 99m (HMPAO-Tc99m) single-photon emission computed tomography, strongly suggest a lateral temporal lobe origin. The genetic analysis found linkage to chromosome 10q, and localized a gene in a 15-cM interval that overlaps a previously found localization for partial epilepsy in a large three-generation family. This syndrome could be called autosomal dominant lateral temporal epilepsy.

Chromosomes, Human, Pair 10↗