Biomedical subjects

Nicolas Molinari

Publications and source records attributed to Nicolas Molinari.

7 recordsLinked to original sources

PubMed2025

Type and position of repeat interruptions as determinants of disease severity and expansion size in Friedreich ataxia.

PURPOSE: In Friedreich ataxia (FRDA) the size of the smaller GAA expansion is a major determinant of disease severity; interruption motifs were identified after the discovery of the pathogenic expansions; however, their impact is only recently investigated. METHODS: 164 patients with FRDA with biallelic expansions and 15 patients without FRDA were analyzed for interruption(s) number, position, and motif. Expansion size and age at onset of ataxia (AAO) were determined for patients with FRDA. RESULTS: Three groups of patients with FRDA were identified by the simultaneous analysis of the precise distance ("depth") between the interruptions (mostly nontriplet) and the 3' end of the expansion (P < .001), the smaller expansion size (P < .001), and AAO (P < .001). Classical FRDA corresponds to absence of interruption or interruption depth < 8 repeats, with AAO often <15 years (area under the curve [AUC] = 0.90; 95% CI, 0.84-0.96); LOFA to interruption depth of 8 to 18 repeats (AUC = 0.97; 95% CI, 0.94-1), with AAO 15 to 34 years (AUC = 1; 95% CI, 1-1); and vLOFA to interruption depth > 18 (AUC = 0.97; 95% CI, 0.92-1), with AAO > 34 years. Multiple (>5) triplet interruptions hamper further expansion. CONCLUSION: This study provides the molecular basis for a novel classification of FRDA that should be recommended for correct diagnosis.

Humans↗

PubMed2006

SPATCLUS: an R package for arbitrarily shaped multiple spatial cluster detection for case event data.

This paper describes an R package, named SPATCLUS that implements a method recently proposed for spatial cluster detection of case event data. This method is based on a data transformation. This transformation is achieved by the definition of a trajectory, which allows to attribute to each point a selection order and the distance to its nearest neighbour. The nearest point is searched among the points which have not yet been selected in the trajectory. Due to the trajectory effects, the distance is weighted by the expected distance under the uniform distribution hypothesis. Potential clusters are located by using multiple structural change models and a dynamic programming algorithm. The double maximum test allows to select the best model. The significativity of potential clusters is determined by Monte Carlo simulations. This method makes it possible the detection of multiple clusters of any shape.

Algorithms↗

PubMed2005

Temporal case clustering in pityriasis rosea: a regression analysis on 1379 patients in Minnesota, kuwait, and diyarbakir, Turkey.

OBJECTIVE: To detect temporal case clustering in patients with pityriasis rosea in different geographic locations. DESIGN: Regression analysis of dates on which 1379 patients were diagnosed as having pityriasis rosea in 3 different geographic locations. The control data consisted of dates of diagnosis of patients with psoriasis in the same settings. SETTING: Dermatology clinics in Kuwait, Minnesota, and Diyarbakir, Turkey.Patients Patients with pityriasis rosea and psoriasis seeking care in the clinics. RESULTS: Three significant positive clusters (P = .005, P =.001, and P =.01, respectively) and 1 significant negative cluster (P<.001) were detected in these series of patients. No cluster was detected in 2 corresponding series of patients with psoriasis in Kuwait and Turkey. CONCLUSION: Temporal case clustering exists in pityriasis rosea.

Adolescent↗

PubMed2004

Molecular epidemiology of DFNB1 deafness in France.

BACKGROUND: Mutations in the GJB2 gene have been established as a major cause of inherited non syndromic deafness in different populations. A high number of sequence variations have been described in the GJB2 gene and the associated pathogenic effects are not always clearly established. The prevalence of a number of mutations is known to be population specific, and therefore population specific testing should be a prerequisite step when molecular diagnosis is offered. Moreover, population studies are needed to determine the contribution of GJB2 variants to deafness. We present our findings from the molecular diagnostic screening of the GJB2 and GJB6 genes over a three year period, together with a population-based study of GJB2 variants. METHODS AND RESULTS: Molecular studies were performed using denaturing High Performance Liquid Chromatograghy (DHPLC) and sequencing of the GJB2 gene. Over the last 3 years we have studied 159 families presenting sensorineural hearing loss, including 84 with non syndromic, stable, bilateral deafness. Thirty families were genotyped with causative mutations. In parallel, we have performed a molecular epidemiology study on more than 3000 dried blood spots and established the frequency of the GJB2 variants in our population. Finally, we have compared the prevalence of the variants in the hearing impaired population with the general population. CONCLUSION: Although a high heterogeneity of sequence variation was observed in patients and controls, the 35delG mutation remains the most common pathogenic mutation in our population. Genetic counseling is dependent on the knowledge of the pathogenicity of the mutations and remains difficult in a number of cases. By comparing the sequence variations observed in hearing impaired patients with those sequence variants observed in general population, from the same ethnic background, we show that the M34T, V37I and R127H variants can not be responsible for profound or severe deafness.

Connexin 26↗

PubMed2003

Case clustering in pityriasis rosea: a multicenter epidemiologic study in primary care settings in Hong Kong.

OBJECTIVES: To investigate the epidemiology of pityriasis rosea in primary care settings in Hong Kong and to analyze for temporal clustering. DESIGN: Retrospective epidemiologic study. SETTING: Six primary care teaching practices affiliated with a university. Patients Forty-one patients with pityriasis rosea, 564 patients with atopic dermatitis (negative control condition), and 35 patients with scabies (positive control condition). METHODS: We retrieved all records of patients with pityriasis rosea, atopic dermatitis, or scabies diagnosed in 3 years. We analyzed temporal clustering by a method based on a regression model. RESULTS: The monthly incidence of pityriasis rosea is negatively but insignificantly correlated with mean air temperature (gamma s = -0.41, P =.19) and mean total rainfall (gamma s = -0.34, P =.27). Three statistically significant clusters with 7, 6, and 7 cases were identified (P =.03), occurring in the second coldest month in the year (February), the second hottest month (July), and a temperate month (April), respectively. For atopic dermatitis (negative control condition), the nonclustering regression model was selected by Akaike information criteria. For scabies (positive control condition), 1 cluster of 20 cases was detected (P =.03). CONCLUSIONS: Significant temporal clustering independent of seasonal variation occurred in our series of patients with pityriasis rosea. This may be indicative of an infectious cause.

Adolescent↗

PubMed2003

Month of birth as a risk factor for narcolepsy.

STUDY OBJECTIVES: A loss of hypocretin neurons has been observed in human narcolepsy; however, the cause of this disorder is still unknown. While family history and genetic factors are important individual risk factors for narcolepsy, environmental factors also contribute to the pathogenesis of the disease. The aim of the study was to find out whether there is a seasonality of month of birth in narcoleptic patients. DESIGN: Diagnosis of narcolepsy with cataplexy was based on International Classification of Sleep Disorders criteria with clinical, standard polysomnographic, and Multiple Sleep Latency Test features. PATIENTS AND SETTING: The birth dates of 886 patients with a clear-cut diagnosis of narcolepsy with cataplexy from 3 large narcolepsy databases (352 from Montpellier-France, 157 from Montreal-Canada, and 377 from Stanford-United States of America) were compared with those of 35,160,522 subjects from the general population. MEASUREMENTS AND RESULTS: Patients with narcolepsy had a significantly different seasonality of month of birth compared to that of the general population. The monthly distribution of birth yielded a peak in March with a maximal odds ratio at 1.45 and a trough in September with a minimal odds ratio at 0.63. No gender or country of origin differences were observed. CONCLUSIONS: A birth seasonality in the development of narcolepsy suggests the presence of environmental factors acting in combination with genetic factors during the fetal or perinatal period, in terms of an autoimmune process targeting the hypocretin system.

Birth Rate↗

PubMed2002

Free knot splines for biochemical data.

The use of spline functions in the analysis of empirical two-dimensional (2-D) data (y(i), x(i)) is described. Spline functions are excellent empirical functions, which can be used with advantage instead of other ones, such as polynomials or exponentials. The knot location seen as variable value corresponds to classical parameter used to describe oxidation curves. An application on characterization of LDL oxidability shows free knot splines in a regression context.

Linear Models↗