RESUMEN
This study focuses on caregivers who work in residential facilities (RFs) for the elderly, and specifically on their organizational citizenship behaviors (OCBs) in relation to their interaction respectively with the overall context (workplace attachment dimension), the spatial-physical environment (perceived environmental comfort), and the social environment (relationship with patients). A sample of health care workers (medical or health care specialists, nurses, and office employees, n = 129) compiled a self-report paper-pencil questionnaire, which included scales measuring the study variables. The research hypotheses included secure workplace attachment style as independent variable, OCBs as the dependent variable, and perceived comfort and relations with patients as moderators. Results showed that both secure workplace attachment and perceived comfort promote OCBs, but the latter counts especially as a compensation of an insecure workplace attachment. As expected, difficult relationships with patients hinder the relationship between secure workplace attachment style and OCBs. In sum, our study highlights the importance of the joint consideration of the psychological, social, and environmental dimensions for fostering positive behaviors in caregivers employed in elderly care settings.
Asunto(s)
Ciudadanía , Lugar de Trabajo , Anciano , Humanos , Cultura Organizacional , Conducta Social , Encuestas y Cuestionarios , Lugar de Trabajo/psicologíaRESUMEN
The present study describes the semantic nature of burnout and engagement in the operators involved in the management of illegal immigration. Semi-structured interviews were conducted on a sample of Italian practitioners (n = 62) of the two levels of the reception system considered: (1) rescue and first aid and (2) reception and integration. Within the framework of the job demands-resources model (JD-R), the interviews deepened the analysis of the positive and negative dimensions of burnout and engagement: exhaustion versus energy, relational deterioration versus relational involvement, professional inefficacy versus professional efficacy and disillusion versus trust. The interviews were analysed using the T-Lab software, through a cluster analysis (bisecting K-means algorithm), which emphasised noteworthy themes. The results show that, in the vast majority of the dimensions considered (for both levels of reception), the same dimensions of engagement of the operators (energy, relational involvement, professional efficacy and trust) are able to lead them into a condition of burnout, with experiences, conversely, of exhaustion, relational deterioration, professional inefficacy and disillusion. These findings expand the knowledge on burnout and engagement in practitioners of illegal immigration, a context characterised by the value of help and welcome.
Asunto(s)
Agotamiento Profesional , Emigración e Inmigración , Agotamiento Psicológico , Humanos , Italia , Mar Mediterráneo , Encuestas y CuestionariosRESUMEN
BACKGROUND: The frequency of Huntington's disease (HD) may vary considerably, with higher estimates in non-Asian populations. We have recently examined the prevalence of HD in the southern part of Sardinia, a large Italian Mediterranean island that is considered a genetic isolate. We observed regional microgeographic differences in the prevalence of HD across the study area similar to those recently reported in other studies conducted in European countries. To explore the basis for this variability, we undertook a study of the incidence of HD in Sardinia over a 10-year period, 2009 to 2018. METHODS: Our research was conducted in the 5 administrative areas of Sardinia island. Case patients were ascertained through multiple sources in Sardinia and Italy. RESULTS: During the incidence period 53 individuals were diagnosed with clinically manifested HD. The average annual incidence rate 2009-2018 was 2.92 per 106 persons-year (95% CI, 2.2 to 3.9). The highest incidence rate was observed in South Sardinia (6.3; 95% CI, 4.2-9.5). This rate was significantly higher (p<0.01) than the rates from Cagliari, Oristano, and Sassari provinces but did not significantly differ (p = 0.38) from the Nuoro rate. CONCLUSIONS: The overall incidence of HD in Sardinia is close to the correspondent estimates in Mediterranean countries. Our findings highlight also the possibility of local microgeographic variations in the epidemiology of HD that might reflect several factors, including a possible founder effect in the rural areas of South Sardinia and Nuoro.
Asunto(s)
Enfermedad de Huntington , Europa (Continente) , Humanos , Enfermedad de Huntington/epidemiología , Incidencia , Italia/epidemiología , PrevalenciaRESUMEN
BACKGROUND: The frequency of Huntington's disease (HD) may vary considerably, with higher estimates in non Asian populations. In Italy, two recent studies performed in Ferrara county and Molise provided different prevalence estimates, varying from 4.2 × 105 to 10.8 × 105. Here we present a study performed in the Southern part of Sardinia, a large Italian mediterranean island that is considered a genetic isolate. METHODS: The study area included the two neighbouring counties of South Sardinia and Cagliari with 353,830 and 431,955 inhabitants respectively on December 31st, 2017 (prevalence date). Case-patients were ascertained through multiple sources in Sardinia and Italy. RESULTS: We identified 54 individuals with HD, of whom 47 were alive on prevalence date. The resulting prevalence rate was 5.98 × 105 in the overall study area, however with marked variations between South Sardinia and Cagliari (9.6 × 105 vs. 3.0 × 105, p = 0.02). In the two study areas, we found similar CAG repeat length in normal alleles (17.5 ± 2.1 vs. 17.7 ± 2.2, p = 0.5). CONCLUSIONS: The overall prevalence of HD in Sardinia is close to the correspondent estimates in Europeans. Our findings also highlighted the possibility of local microgeographic variations in the epidemiology of HD.
Asunto(s)
Enfermedad de Huntington/epidemiología , Adulto , Anciano , Femenino , Humanos , Italia/epidemiología , Masculino , Islas del Mediterráneo/epidemiología , Persona de Mediana Edad , PrevalenciaRESUMEN
This study assesses the levels of and relationships between the Motivation to donate, Job crafting propensity, and the Organizational citizenship behavior of blood collection volunteers in a non-profit association. An Italian sample of AVIS (the Italian Association of Voluntary Blood donors) blood donors (N = 1215) actively involved in organizing blood collection, were asked to complete the Italian version of the Volunteer Function Index, the Job crafting scale, and the Organizational citizenship behavior scale. The tools were verified by Confirmatory factor analysis and their relationships were explored using Structural equation modeling for hidden variables. The three constructs have overall high scores. Motivation to donate and Job crafting show a clear correlation, with the latter influencing volunteer Organizational citizenship behavior. The study highlights the need to take into consideration the Motivation to donate, Job crafting and Organizational citizenship behavior of volunteers, particularly in countries such as Italy, where blood collection is almost exclusively carried out thanks to spontaneous, altruistic, and disinterested commitment.
Asunto(s)
Motivación , Cultura Organizacional , Organizaciones sin Fines de Lucro , Voluntarios , Femenino , Humanos , Italia , Satisfacción en el Trabajo , Masculino , Organizaciones sin Fines de Lucro/estadística & datos numéricos , Encuestas y Cuestionarios , Voluntarios/estadística & datos numéricosAsunto(s)
Apraxias/genética , Proteína C9orf72/genética , Expansión de las Repeticiones de ADN/genética , Anciano , Apatía , Apraxias/complicaciones , Apraxias/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Femenino , Humanos , Hipocinesia/complicaciones , Imagen por Resonancia Magnética , Neuroimagen , Pruebas NeuropsicológicasRESUMEN
We investigated intrafamilial phenotypic variability in carriers of the C9orf72 mutation, analysing clinical, neuropsychological and imaging characteristics of various members from a large Sardinian kindred with FTD or ALS. We compared these with those of C9 + patients in our ALS and FTD cohorts. Results showed that three patients carried the C9orf72 mutation: two with ALS and one with FTD and Parkinsonism. C9 + patients in our bvFTD Sardinian cohort had a higher frequency of Parkinsonism than non-mutated patients (75% vs. 36.3%, p <0.02). Parkinsonism was present in 2.7% of our ALS cohort and 3.3% of the C9 + patients. The prevalence of Parkinsonism in C9 + patients in the bvFTD and ALS cohorts showed a statistically significant difference (p <0.006). In conclusion, Parkinsonism was frequently associated with FTD but not ALS in a large Sardinian family, a finding reflected in the wider C9orf72 associated Sardinian ALS and FTD populations.
Asunto(s)
Esclerosis Amiotrófica Lateral/genética , Salud de la Familia , Demencia Frontotemporal/genética , Mutación/genética , Proteínas/genética , Anciano , Esclerosis Amiotrófica Lateral/diagnóstico por imagen , Ataxina-2/genética , Proteína C9orf72 , Estudios de Cohortes , Femenino , Demencia Frontotemporal/complicaciones , Demencia Frontotemporal/diagnóstico por imagen , Genotipo , Humanos , Italia/epidemiología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Trastornos Parkinsonianos/etiología , Fenotipo , Proteínas tau/genéticaRESUMEN
The hexanucleotide repeat expansion GGGGCC in the C9ORF72 gene larger than 30 repeats has been identified as a major genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Recent papers investigated the possible pathogenic role and associated clinical phenotypes of intermediate C9ORF72 repeat expansion ranging between 20 and 30 repeats. Some studies suggested its pathogenicity for typical Parkinson's disease (PD), atypical parkinsonian syndromes, FTD with/without parkinsonism, and ALS with/without parkinsonism or with/without dementia. In our study, we aimed to screen patients affected by atypical parkinsonian syndromes or PD complicated by psychosis or dementia for the presence of C9ORF72 repeat expansions, and in unrelated age- and sex-matched healthy controls. Consecutive unrelated patients with atypical parkinsonian syndromes and patients with PD complicated by psychosis or dementia were included in this study. Atypical parkinsonian syndromes were further divided into two groups: one with patients who met the criteria for the classic forms of atypical parkinsonism [multiple system atrophy (MSA), Lewy body disease (LBD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD)] ;and patients who did not meet the above criteria, named non-classical atypical parkinsonism with or without dementia. Ninety-two unrelated patients (48 men, 44 women) were enrolled. None of the patients was found to be carriers of C9ORF72 repeat expansions with more than 30 repeats. Intermediate 20-30 repeat expansions were detected in four female patients (4.3 %). Three of them presented clinical features of atypical parkinsonian syndromes, two with non-classical atypical parkinsonism and dementia FTD-like, and one with non-classical atypical parkinsonism without dementia. The other patient presented clinical features of typical PD complicated by psychosis. Among 121 control subjects, none presented long or short expansion for the C9ORF72 gene. Our findings seem to support the hypothesis that the hexanucleotide expansions of C9ORF72 gene with intermediate repetitions between 20 and 29 repetitions could be associated with typical PD with psychosis or dementia and atypical parkinsonisms with dementia (non-classical atypical parkinsonism with dementia FTD-like) or without dementia (non-classical atypical parkinsonism upper MND-like), although the causal relationship is still unclear. In these latter patients, parkinsonism, more or less levodopa responsive, constituted the symptomatological central core at onset.
Asunto(s)
Demencia/genética , Enfermedad de Parkinson/genética , Trastornos Parkinsonianos/genética , Proteínas/genética , Trastornos Psicóticos/genética , Adulto , Anciano , Anciano de 80 o más Años , Proteína C9orf72 , Comorbilidad , Expansión de las Repeticiones de ADN , Demencia/epidemiología , Femenino , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/epidemiología , Trastornos Parkinsonianos/epidemiología , Trastornos Psicóticos/epidemiologíaRESUMEN
In our study we analysed clinical and neuropsychological data in a cohort of 57 Sardinian patients with FTD (55 apparently unrelated and two belonging to the same family), who underwent genetic screening for the C9orf72 mutation. Eight out of 56 patients were found positive for the C9orf72 mutation representing 14% of the entire cohort and 31.6% of the familial cases (6/19). C9orf72 mutated patients differed from the other FTD cases of the cohort for a younger age of onset, higher frequency of familial history for FTD and higher prevalence of delusional psychotic symptoms and hallucinations. In the neuropsychological assessment, C9orf72 mutated patients differed from non-mutated for the high frequency of visuospatial dysfunction regarding constructional apraxia (p = 0.02). In conclusion, our study confirms that Sardinian FTD patients have peculiar genetic characteristics and that C9orf72 mutated patients have a distinctive clinical and neuropsychological profile that could help differentiate them from other FTD patients. In our cohort we found that constructional apraxia, rarely reported in FTD, can properly discriminate between C9orf72 mutated and non-mutated patients and contribute to broaden the neuropsychological profile in frontotemporal dementia associated with this mutation.
Asunto(s)
Apraxias/etiología , Apraxias/genética , Demencia Frontotemporal/complicaciones , Demencia Frontotemporal/genética , Mutación/genética , Proteínas/genética , Anciano , Encéfalo/diagnóstico por imagen , Proteína C9orf72 , Estudios de Cohortes , Femenino , Demencia Frontotemporal/diagnóstico por imagen , Estudios de Asociación Genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Trastornos de la Percepción/etiología , Trastornos de la Percepción/genética , Fenotipo , Estimulación Luminosa , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
It has been shown that different genes could be associated with distinctive clinical and radiological phenotypes of FTD. TARDBP gene has been described worldwide in few cases of FTD so its phenotype is still unclear. The objective is to study the clinical and radiological characteristics of TARDBP-related FTD. In the present study, we report clinical, neuropsychological and radiological features of five new Sardinian non-related cases of FTD carriers of the p.A382T TARDBP mutation. Furthermore, we reviewed non-related FTD cases with TARDBP mutations previously described in literature. The p.A382T missense mutation of TARDBP was present in the 21.7 % of familial cases of our FTD cohort (5/23) and in no one of the sporadic patients. 3 of 5 patients showed a temporal variant FTD and 4/5 a predominant temporal involvement at MRI. The review of the literature of FTD cases with TARDBP mutations showed that in 5 of 16 cases, the clinical phenotype was consistent with temporal variant of FTD or semantic dementia (31 %) and in 7 of 16 cases neuroimaging showed predominant temporal lobe involvement (43.7 %). Our study further supports the pathogenetic role of TARDBP mutations in pure FTD and in the full spectrum of FTD/ALS. The presence of a predominant temporal lobe involvement in a high percentage of FTD mutated patients with a peculiar clinical pattern could be useful in the differential diagnosis with other forms of dementia/FTD both sporadic and familial.
Asunto(s)
Esclerosis Amiotrófica Lateral/genética , Esclerosis Amiotrófica Lateral/patología , Proteínas de Unión al ADN/genética , Demencia Frontotemporal/genética , Demencia Frontotemporal/patología , Mutación , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Linaje , FenotipoRESUMEN
Based on our previous finding of the p.A382T founder mutation in ALS patients with concomitant parkinsonism in the Sardinian population, we hypothesized that the same variant may underlie Parkinson's disease (PD) and/or other forms of degenerative parkinsonism on this Mediterranean island. We screened a cohort of 611 patients with PD (544 cases) and other forms of degenerative parkinsonism (67 cases) and 604 unrelated controls for the c.1144G > A (p.A382T) missense mutation of the TARDBP gene. The p.A382T mutation was identified in nine patients with parkinsonism. Of these, five (0.9 % of PD patients) presented a typical PD (two with familiar forms), while four patients (6.0 % of all other forms of parkinsonism) presented a peculiar clinical presentation quite different from classical atypical parkinsonism with an overlap of extrapyramidal-pyramidal-cognitive clinical signs. The mutation was found in eight Sardinian controls (1.3 %) consistent with a founder mutation in the island population. Our findings suggest that the clinical presentation of the p.A382T TARDBP gene mutation may include forms of parkinsonism in which the extrapyramidal signs are the crucial core of the disease at onset. These forms can present PSP or CBD-like clinical signs, with bulbar and/or extrabulbar pyramidal signs and cognitive impairment. No evidence of association has been found between TARDBP gene mutation and typical PD.
Asunto(s)
Esclerosis Amiotrófica Lateral/genética , Proteínas de Unión al ADN/genética , Predisposición Genética a la Enfermedad/genética , Mutación/genética , Enfermedad de Parkinson/genética , Anciano , Femenino , Pruebas Genéticas/métodos , Genotipo , Humanos , Italia , Masculino , Persona de Mediana Edad , FenotipoAsunto(s)
Trastorno Bipolar/genética , Demencia Frontotemporal/genética , Mutación/genética , Proteínas/genética , Trastorno Bipolar/complicaciones , Trastorno Bipolar/diagnóstico por imagen , Trastorno Bipolar/patología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Proteína C9orf72 , Demencia Frontotemporal/complicaciones , Demencia Frontotemporal/diagnóstico por imagen , Demencia Frontotemporal/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Radiofármacos , Exametazima de Tecnecio Tc 99m , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
Vitamin D response elements (VDREs) have been found in the promoter region of the MS-associated allele HLA-DRB1*15:01, suggesting that with low vitamin D availability VDREs are incapable of inducing *15:01 expression allowing in early life autoreactive T-cells to escape central thymic deletion. The Italian island of Sardinia exhibits a very high frequency of MS and high solar radiation exposure. We test the contribution of VDREs analysing the promoter region of the MS-associated DRB1 *04:05, *03:01, *13:01 and *15:01 and non-MS-associated *16:01, *01, *11, *07:01 alleles in a cohort of Sardinians (44 MS patients and 112 healthy subjects). Sequencing of the DRB1 promoter region revealed a homozygous canonical VDRE in all *15:01, *16:01, *11 and in 45/73 *03:01 and in heterozygous state in 28/73 *03:01 and all *01 alleles. A new mutated homozygous VDRE was found in all *13:03, *04:05 and *07:01 alleles. Functionality of mutated and canonical VDREs was assessed for its potential to modulate levels of DRB1 gene expression using an in vitro transactivation assay after stimulation with active vitamin D metabolite. Vitamin D failed to increase promoter activity of the *04:05 and *03:01 alleles carrying the new mutated VDRE, while the *16:01 and *03:01 alleles carrying the canonical VDRE sequence showed significantly increased transcriptional activity. The ability of VDR to bind the mutant VDRE in the DRB1 promoter was evaluated by EMSA. Efficient binding of VDR to the VDRE sequence found in the *16:01 and in the *15:01 allele reduced electrophoretic mobility when either an anti-VDR or an anti-RXR monoclonal antibody was added. Conversely, the Sardinian mutated VDRE sample showed very low affinity for the RXR/VDR heterodimer. These data seem to exclude a role of VDREs in the promoter region of the DRB1 gene in susceptibility to MS carried by DRB1* alleles in Sardinian patients.
Asunto(s)
Alelos , Cadenas HLA-DRB1/genética , Esclerosis Múltiple/genética , Elemento de Respuesta a la Vitamina D/genética , Adulto , Secuencia de Bases , Estudios de Casos y Controles , Biología Computacional , Femenino , Predisposición Genética a la Enfermedad/genética , Humanos , Italia , Masculino , Datos de Secuencia Molecular , Receptores de Calcitriol/metabolismo , Análisis de Secuencia de ADN , Activación Transcripcional/genéticaRESUMEN
Mutations in LRRK2 represent the most common causes of Parkinson's disease (PD) identified to date, but their penetrance is incomplete and probably due to the presence of other genetic or environmental factors required for development of the disease. We analyzed the presence of parkin sequence variants (mutations or polymorphisms) and exon rearrangements in LRRK2 mutations carriers (both PD patients and unaffected relatives) in order to detect a possible modifier effect on penetrance. Eight families with nine PD patients with heterozygous LRRK2 mutations (identified within 380 Sardinian PD patients screened for the presence of the five most common LRRK2 mutations) and sixteen additional relatives were genetically investigated for the presence of LRRK2 and parkin mutations. No evidence was found for the presence of pathological parkin mutations or exon rearrangements in patients or not affected family members. Three single-nucleotide polymorphisms (SNPs) were identified both in patients and unaffected relatives but did not significantly differ between the two groups. These data provide no support to the hypothesis whereby such parkin gene mutations may be commonly implicated in possible effect on penetrance in LRRK2 mutation carriers.
RESUMEN
Mutations in the LRRK2 gene are the most common known cause of familial and sporadic Parkinson's disease (PD). Few studies performed to date to assess frequency of these mutations are actually only representative of specific areas. Here we study the frequency and clinical phenotype of LRRK2 G2019S, I2020T and R1441C/G/H mutations in 356 Sardinian patients with idiopathic PD and 208 controls. Seventeen additional subjects, relatives of PD mutated probands, were enrolled. Eight patients were mutated in heterozygosis for LRRK2 gene (2.3%): six carried the G2019S (1.7%) and two the R1441C (0.6%) mutation. Three PD patients G2019S carriers (50%) were detected in two contiguous villages comprising 3921 inhabitants while the other three (50%) were identified in the remaining population of 796,079 inhabitants. Only one mutated proband had a family history of PD. LRRK2 G2019S and R1441C mutations associated with PD were not an uncommon mutation in a Sardinian population, especially in sporadic PD patients. The detection of the G2019S variant in ten unaffected relatives confirms a reduced penetrance of the underlying mutation and might explain its prevalence among patients with sporadic PD. These findings may provide new insights into the importance of studies of frequency of LRKK2 mutations in PD patients originating from small ethnically homogeneous populations.
Asunto(s)
Cisteína/genética , Predisposición Genética a la Enfermedad , Glicina/genética , Mutación/genética , Enfermedad de Parkinson/genética , Proteínas Serina-Treonina Quinasas/genética , Serina/genética , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Arginina/genética , Análisis Mutacional de ADN , Femenino , Frecuencia de los Genes , Pruebas Genéticas , Genotipo , Humanos , Italia , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/diagnóstico por imagen , Grupos de Población/genética , Tomografía Computarizada de Emisión de Fotón Único/métodosRESUMEN
BACKGROUND: The Mediterranean island of Sardinia has a strikingly high incidence of the autoimmune disorders Type 1 Diabetes (T1D) and Multiple Sclerosis (MS). Furthermore, the two diseases tend to be co-inherited in the same individuals and in the same families. These observations suggest that some unknown autoimmunity variant with relevant effect size could be fairly common in this founder population and could be detected using linkage analysis. METHODS: To search for T1D and MS loci as well as any that predispose to both diseases, we performed a whole genome linkage scan, sequentially genotyping 593 microsatellite marker loci in 954 individuals distributed in 175 Sardinian families. In total, 413 patients were studied; 285 with T1D, 116 with MS and 12 with both disorders. Model-free linkage analysis was performed on the genotyped samples using the Kong and Cox logarithm of odds (LOD) score statistic. RESULTS: In T1D, aside from the HLA locus, we found four regions showing a lod-score > or =1; 1p31.1, 6q26, 10q21.2 and 22q11.22. In MS we found three regions showing a lod-score > or =1; 1q42.2, 18p11.21 and 20p12.3. In the combined T1D-MS scan for shared autoimmunity loci, four regions showed a LOD >1, including 6q26, 10q21.2, 20p12.3 and 22q11.22. When we typed more markers in these intervals we obtained suggestive evidence of linkage in the T1D scan at 10q21.2 (LOD = 2.1), in the MS scan at 1q42.2 (LOD = 2.5) and at 18p11.22 (LOD = 2.6). When all T1D and MS families were analysed jointly we obtained suggestive evidence in two regions: at 10q21.1 (LOD score = 2.3) and at 20p12.3 (LOD score = 2.5). CONCLUSION: This suggestive evidence of linkage with T1D, MS and both diseases indicates critical chromosome intervals to be followed up in downstream association studies.
Asunto(s)
Diabetes Mellitus Tipo 1/genética , Ligamiento Genético , Predisposición Genética a la Enfermedad , Repeticiones de Microsatélite/genética , Esclerosis Múltiple/genética , Adolescente , Adulto , Niño , Mapeo Cromosómico , Diabetes Mellitus Tipo 1/complicaciones , Femenino , Marcadores Genéticos/genética , Haplotipos , Humanos , Masculino , Islas del Mediterráneo , Persona de Mediana Edad , Esclerosis Múltiple/complicaciones , Sitios de Carácter Cuantitativo , Estadísticas no ParamétricasRESUMEN
BACKGROUND: Multiple sclerosis (MS) is consistently associated with particular HLA-DRB1-DQB1 haplotypes. However, existing evidence suggests that variation at these loci does not entirely explain association of the HLA region with the disease. The MOG locus is a prime positional and functional candidate for such additional predisposing effects but the analysis is complicated by the strong, albeit labyrinthine pattern of linkage disequilibrium in the region. Here we have assessed the association of MOG variation with MS in the Sardinian population to see if it represents an independent contributor to MS predisposition. RESULTS: After re-sequencing the MOG gene in 21 healthy parents of MS patients we detected 134 variants, 33 of which were novel. A set of 40 informative SNPs was then selected and assessed for disease association together with 1 intragenic microsatellite in an initial data set of 239 MS families. This microsatellite and 11 SNPs were found to be positively associated with MS, using the transmission disequilibrium test, and were followed up in an additional 158 families (total families analysed = 397). While in these 397 families, 8 markers showed significant association with MS, through conditional tests we determined that these MOG variants were not associated with MS independently of the main DRB1-DQB1 disease associations. CONCLUSION: These results indicate that variation within the MOG gene is not an important independent determinant of MS-inherited risk in the Sardinian population.