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Maria Giovanna Marrosu

Publications and source records attributed to Maria Giovanna Marrosu.

15 recordsLinked to original sources
PubMed2006

Linkage disequilibrium screening for multiple sclerosis implicates JAG1 and POU2AF1 as susceptibility genes in Europeans.

By combining all the data available from the Genetic Analysis of Multiple sclerosis in EuropeanS (GAMES) project, we have been able to identify 17 microsatellite markers showing consistent evidence for apparent association. As might be expected five of these markers map within the Major Histocompatibility Complex (MHC) and are in LD with HLA-DRB1. Individual genotyping of the 12 non-MHC markers confirmed association for three of them--D11S1986, D19S552 and D20S894. Association mapping across the candidate genes implicated by these markers in 937 UK trio families revealed modestly associated haplotypes in JAG1 (p=0.019) on chromosome 20p12.2 and POU2AF1 (p=0.003) on chromosome 11q23.1.

Calcium-Binding Proteins↗
PubMed2006

Hypersexual behaviour, frotteurism and delusional jealousy in a young parkinsonian patient during dopaminergic therapy with pergolide: A rare case of iatrogenic paraphilia.

Neuropsychological and psychopathological modifications induced by dopaminergic drugs in patients with Parkinson's disease (PD) are invariably not taken into sufficient consideration by the neurologist. Among the former, modifications of sexual urges and behaviours are of particular importance with regard to severity and variety of clinical pictures. Although rare, such modifications may assume the connotations of an aberrant sexual behaviour with criminal implications, in line with a diagnosis of paraphilia. The authors report the case of a 51-year-old male PD patient who, after a few years of dopaminergic treatment with pergolide, developed a paraphilic disorder, consistent with DSM-IV TR diagnosis of frotteurism, and delusional jealousy. The patient presented mild motor impairment and lack of or negligible cognitive deterioration, thus providing evidence that these disorders are not typical of advanced PD. Pergolide was reduced and quetiapine, an atypical neuroleptic, was introduced with subsequent subsiding of the paraphilic disorder and improvement of delusional jealousy.

Age of Onset↗
PubMed2006

Imaging brain damage in first-degree relatives of sporadic and familial multiple sclerosis.

OBJECTIVE: Our objective was to assess brain damage in first-degree relatives of patients with sporadic and familial multiple sclerosis (MS). METHODS: Asymptomatic first-degree relatives of sporadic (sMS, n = 152) and familial MS (fMS, n = 88) and healthy volunteers (NC, n = 56) underwent brain MRI and magnetization transfer (MT) imaging on a mobile MR scan. On MR examinations, we visually assessed white matter (WM) lesions and quantified WM lesion volumes, brain volumes, and MT ratio (MTr) in lesions and normal-appearing WM (NAWM). RESULTS: A lesional MR pattern similar to that of MS patients was found in 4% sMS and 10% fMS. In these WM lesions, MTr was lower (p < 0.0001) than in the WM of NC. In contrast, there was no difference in NAWM-MTr and brain volume values between the three groups. INTERPRETATION: Focal brain abnormalities indistinguishable from those of MS occur in asymptomatic first-degree relatives of MS patients. These are twice more frequent in fMS than in sMS but do not lead to the widespread tissue damage commonly found in MS patients. Although there is a genetic susceptibility to develop brain abnormalities suggestive of focal demyelination in first-degree relatives of MS patients, other factors are probably critical for the development of a diffuse, clinically relevant, pathology.

Adult↗
PubMed2006

Prevalence of primary blepharospasm in Sardinia, Italy: a service-based survey.

We performed a service-based epidemiological study of primary blepharospasm in the island of Sardinia (Italy). Due to its favorable geographical location, we are confident we will provide reliable data from patients seeking botulinum toxin treatment. A total of 53 patients were assessed. Prevalence was estimated to be 32.2 per 1 million (95% confidence interval, 23.0-40.8). These results are in line with those obtained in other similar surveys, that is, record-based, and performed in various European regions such as Northern England, the Munich area, as well as the Epidemiologic Study of Dystonia in Europe.

Adult↗
PubMed2004

The co-inheritance of type 1 diabetes and multiple sclerosis in Sardinia cannot be explained by genotype variation in the HLA region alone.

Type 1 diabetes (T1D) and multiple sclerosis (MS) are two autoimmune diseases which exhibit a considerably higher incidence in Sardinia compared with the surrounding southern European populations. Surprisingly, a 5-fold increased prevalence of T1D has also been observed in Sardinian MS patients. Susceptibility to both disorders is associated with common variants of the HLA-DRB1 and -DQB1 loci. In this study, we determined the relative contribution of genotype variation of these loci to the co-occurrence of the two disorders in Sardinia. We genotyped 1052 T1D patients and 1049 MS patients (31 of whom also had T1D) together with 1917 ethnically matched controls. On the basis of the absolute risks for T1D of the HLA-DRB1-DQB1 genotypes, we established that these loci would only contribute to a 2-fold increase in T1D prevalence in MS patients. From this evidence, we conclude that shared disease associations due to the HLA-DRB1-DQB1 loci provide only a partial explanation for the observed increased prevalence of T1D in Sardinian MS patients. The data suggest that variation at other non-HLA class II loci, and/or unknown environmental factors contribute significantly to the co-occurrence of these two traits.

Adolescent↗
PubMed2004

PTPRC (CD45) C77G mutation does not contribute to multiple sclerosis susceptibility in Sardinian patients.

A linkage and association of the CD45 (protein-tyrosine phosphatase, receptor-type C) C77G polymorphism and multiple sclerosis (MS) has been found in some studies but not in others. We analysed the C77G polymorphism in MS patients from the genetically homogeneous population of Sardinia. Using the transmission disequilibrium test, the mutation has been sought in 241 patients and 217 healthy sibs (HS) from singleton MS families and it was found in 5 (2.07 %) affected and 3 (1.38%) HS from 7 heterozygous parents (1.45 %). Transmission of the G77 allele was 71.4 % (TDT = 1.3, P = 0.26) in patients and 50% (TDT = 0, P = 1) in HS. Stratifying families according to carriage of MS-predisposing (DR+) or not-predisposing (DR-) HLA-DR-DQ genotype in patients, percentage of G77 transmission to DR+ patients was 33 (TDT = 0.33, P = 0.56, Pc = 1.12), while it was 100 (TDT = 4, P = 0.045, Pc = 0.09) in the DR-patients. We concluded that, despite the presence of CD45 G77 polymorphism in a few patients who did not carry the HLADR- DQ MS-predisposing molecules, CD45 did not contribute to development of the disease in Sardinian MS.

Alleles↗
PubMed2004

Heterogeneity in the magnitude of the insulin gene effect on HLA risk in type 1 diabetes.

There is still uncertainty concerning the joint action of the two established type 1 diabetes susceptibility loci, the HLA class II DQB1 and DRB1 genes (IDDM1) and the insulin gene (INS) promoter (IDDM2). Some previous studies reported independence, whereas others suggested heterogeneity in the relative effects of the genotypes at these disease loci. In this study, we have assessed the combined effects of the HLA-DQB1/DRB1 and INS genotypes in 944 type 1 diabetic patients and 1,023 control subjects, all from Sardinia. Genotype variation at INS significantly influenced disease susceptibility in all HLA genotype risk categories. However, there was a significant heterogeneity (P = 2.4 x 10(-4)) in the distribution of the INS genotypes in patients with different HLA genotypes. The INS predisposing genotype was less frequent (74.9%) in high-risk HLA genotype-positive patients than in those with HLA intermediate-risk (86.1%) and low-risk (84.8%) categories. Gene-gene interaction modeling led to rejection of the additive model, whereas a multiplicative model showed a better, albeit still partial, fit to the observed data. These genetic results are consistent with an interaction between the protein products of the HLA and INS alleles, in which both the affinity of the various HLA class II molecules for a preproinsulin-derived peptide and the levels of this peptide in the thymus act jointly as key regulators of type 1 diabetes autoimmunity.

Diabetes Mellitus, Type 1↗
PubMed2003

Allogeneic hematopoietic stem cell transplantation in a patient affected by large granular lymphocyte leukemia and multiple sclerosis.

We describe a 57-year-old man, affected by large granular lymphocyte (LGL) leukemia and concomitant primary progressive multiple sclerosis (MS), treated with allogeneic hematopoietic stem cell transplantation (HSCT) from an HLA-identical sibling. The patient was conditioned with fludarabine, busulphan, and cyclophosphamide. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and short-term methotrexate. At 3 years follow-up, the patient is in complete remission of LGL with a marked improvement in neurological conditions. This is the first case of allogeneic HSCT in a patient with LGL leukemia and concomitant primary progressive MS. Allogeneic HSCT, performed in our patient to cure the lymphoproliferative disorder, improved the clinical course of MS.

Follow-Up Studies↗
PubMed2003

Refining the linkage analysis on chromosome 10 in 449 sib-pairs with multiple sclerosis.

Genome-wide screens for linkage in multiplex families with multiple sclerosis (MS) from United Kingdom, Sardinia, Italy and the Nordic countries (Denmark, Finland, Norway and Sweden) have each shown suggestive or potential linkage on chromosome 10. The partially overlapping regions identified by these studies encompass around 60 cM of the chromosome. In order to explore this region further, we typed 13 microsatellite markers in the same 449 families originally studied in the individual screens. This additional genotyping increased the information extraction in the region from 52% to 79% and revealed increased support for linkage (MLS 2.5) peaking at 10p15.

Alleles↗
PubMed2003

A genome-wide screen for linkage disequilibrium in Sardinian multiple sclerosis.

Using indirect whole genome association screening, we have searched for multiple sclerosis susceptibility genes in the genetically isolated high risk Sardinian population. Two screens were performed; the first was based on 229 cases and 264 unrelated controls, and the second on 235 trio families. Each screen employed a dense set of microsatellite markers and DNA pooling. Data from both screens were available from 2764 markers. Nine markers showed nominally significant results in both screens independently. Five of these markers-D2S408 (2q36), D6S271 (6p21), D6S344 (6p25), D7S1818 (7p12) and D16S420 (16p12)-remained nominally significant in both studies after conservative refining analysis.

Adult↗
PubMed2002

Patients with multiple sclerosis and risk of type 1 diabetes mellitus in Sardinia, Italy: a cohort study.

BACKGROUND: Individuals from Sardinia, Italy, are at high risk of developing multiple sclerosis and type 1 diabetes mellitus. We attempted to assess the prevalence in this region of type 1 diabetes mellitus in individuals with multiple sclerosis, and to ascertain disease risk factors. METHODS: We did a cohort study to assess prevalence of type 1 diabetes in 1090 people with multiple sclerosis, and in their parents (n=2180) and siblings (n=3300), all born and living in Sardinia. All participants were patients at the multiple sclerosis clinic in Cagliari, and were judged representative of the total Sardinian outpatients and inpatients. We asked patients whether their parents or siblings had multiple sclerosis or diabetes, confirming replies by examining clinical records. We identified risk factors for diabetes with univariate and multivariate logistic regression analyses. FINDINGS: Diabetes prevalence in people with multiple sclerosis was, respectively, about three-fold and five-fold that in their healthy siblings (p=0.001) and in the general population (p<0.0001). Presence of other relatives with multiple sclerosis conferred increased risk of type 1 diabetes to healthy siblings of individuals with multiple sclerosis (odds ratio=3.41, p=0.0019). Diabetes risk was six-fold higher in patients with relatives having multiple sclerosis than in healthy siblings of multiple sclerosis patients without other relatives with the disease (p=0.0001). INTERPRETATION: In Sardinian families with genetic inheritance of multiple sclerosis type 1 diabetes is prevalent, both in multiple sclerosis patients and in healthy siblings. This finding indicates that common genes contribute to susceptibility to both diseases in this population.

Adolescent↗
PubMed2002

Age-related disability in multiple sclerosis.

There is evidence that the clinical course of multiple sclerosis is age related. The present study evaluated the relationship between age and rate of disability progression in a large hospital-based cohort of definite cases of multiple sclerosis (n= 1,463). Patients were followed every 6 to 12 months for a total period of observation of 11,387.8 person-years. Expanded Disability Status Scale scores increased significantly with increasing current age and longer duration of disease (p=0.007). Median times to reach Expanded Disability Status Scale scores of 4.0 and 6.0, assessed using an extended Kaplan-Meier method with age as a categorical time-varying covariate, were significantly longer among patients aged 20 to 35 years compared with patients aged 36 to 50 and 51 to 65 years (p < 0.0001). Significant associations were observed between mean Expanded Disability Status Scale scores and age at disease onset, current age, and the interaction of age at disease onset and current age (p < 0.001). Current age had a greater effect (59% of variability in the model) on disease severity than did age at disease onset. Furthermore, a multiplicative effect on Expanded Disability Status Scale score was observed for age at disease onset and current age combined, indicating a faster rate of disease progression in older patients. In conclusion, the results of the current study demonstrate the impact of age on rate of disability progression in multiple sclerosis and suggest that an age-adjusted progression index may be a more relevant criterion for defining differences between multiple sclerosis groups.

Adult↗
PubMed2002

Lack of evidence for a role of the myelin basic protein gene in multiple sclerosis susceptibility in Sardinian patients.

A link between myelin basic protein (MBP) polymorphism and multiple sclerosis (MS) has been reported in some populations but not in others. We analysed two polymorphisms in the 5' flanking region of the MBP exon 1 gene in MS patients from the founder population of Sardinia. Using the transmission disequilibrium test (TDT), MBP polymorphisms were analysed in 363 singleton MS families. No distortion in transmission of the tetranucleotide repeat (ATGG)12 and of the 1116-1540 nt alleles was found. Moreover, we discovered no epistatic effect of the MBP gene on the HLA/MHC DRB1,DQB1, DPB1 loci or on alleles defined by D6S1683 marker found to be associated with MS in Sardinians. We concluded that the MBP gene does not play a role in MS susceptibility in Sardinians.

Adolescent↗
PubMedDate not supplied

Effect of dose and frequency of interferon beta-1a administration on clinical and magnetic resonance imaging parameters in relapsing-remitting multiple sclerosis.

There is still debate over the optimal dosage, frequency and route of administration of interferon (IFN) beta in multiple sclerosis (MS). A prospective, non-randomized, comparative study was performed to evaluate differences in magnetic resonance imaging and clinical outcomes of two IFN beta-1a preparations (30mcg intramuscular [im] once-weekly [qw], AVO; and 22 mcg subcutaneous [sc] three-times-weekly [tiw]; R22). Relapsing-remitting MS patients on one of the two IFN preparations (AVO, n=47; R22, n=48) were assessed at baseline and after 6 months of further treatment. There were no significant differences between the two groups at baseline. Both groups showed significantly reduced relapse rates (F=19.5; p<0.001) from baseline (0.6) to 6-month assessment (0.2; p<0.001). Univariate analysis showed a significant difference in favour of R22 on T2 lesion volume (F=14.4; p<0.001) and T1 black hole lesion load (F=8.5; p=0.004), the latter showing a significant increase in the AVO group (p<0.001). The incidence of patients with new T1 black holes was also higher for AVO than R22 (23.5% vs 8.3%; p=0.025). These results from patients receiving AVO or R22 in normal clinical practice are in line with randomized clinical studies that show the benefits of high-dose, high-frequency administration of IFN beta-1a in MS therapy.

Adjuvants, Immunologic↗