Biomedical subjects

Josette Mancini

Publications and source records attributed to Josette Mancini.

7 recordsLinked to original sources

PubMed2006

The incidence of Rett syndrome in France.

Since the description of Rett syndrome, only a handful of epidemiologic studies based only on clinical investigation have been reported. Mutations in the MECP2 gene are associated with Rett syndrome and French laboratories have organized a clinical and molecular network to investigate the incidence of Rett syndrome in France including the results of molecular investigations. The present study, based on a large cohort of 424 patients with Rett syndrome, found that the incidence of this disease with a MECP2 mutation varied between 0.43 to 0.71 per 10,000 females. The total population of females aged 4-15 years in November 2004 in France was estimated to be 4,337,627. The data presented here indicate a prevalence of Rett syndrome of 0.558 per 10,000 females aged 4-15 years in France. The incidence of Rett syndrome is in accordance with other European epidemiologic studies based on clinical examination. Given that this is a minimum incidence because complete inventory was not possible, this study of patients with Rett syndrome reinforces the fact that the great majority of patients with Rett syndrome have a MECP2 mutation.

Adolescent↗

PubMed2005

Mecp2 deficiency disrupts norepinephrine and respiratory systems in mice.

Rett syndrome is a severe X-linked neurological disorder in which most patients have mutations in the methyl-CpG binding protein 2 (MECP2) gene and suffer from bioaminergic deficiencies and life-threatening breathing disturbances. We used in vivo plethysmography, in vitro electrophysiology, neuropharmacology, immunohistochemistry, and biochemistry to characterize the consequences of the MECP2 mutation on breathing in wild-type (wt) and Mecp2-deficient (Mecp2-/y) mice. At birth, Mecp2-/y mice showed normal breathing and a normal number of medullary neurons that express tyrosine hydroxylase (TH neurons). At approximately 1 month of age, most Mecp2-/y mice showed respiratory cycles of variable duration; meanwhile, their medulla contained a significantly reduced number of TH neurons and norepinephrine (NE) content, even in Mecp2-/y mice that showed a normal breathing pattern. Between 1 and 2 months of age, all unanesthetized Mecp2-/y mice showed breathing disturbances that worsened until fatal respiratory arrest at approximately 2 months of age. During their last week of life, Mecp2-/y mice had a slow and erratic breathing pattern with a highly variable cycle period and frequent apneas. In addition, their medulla had a drastically reduced number of TH neurons, NE content, and serotonin (5-HT) content. In vitro experiments using transverse brainstem slices of mice between 2 and 3 weeks of age revealed that the rhythm produced by the isolated respiratory network was irregular in Mecp2-/y mice but could be stabilized with exogenous NE. We hypothesize that breathing disturbances in Mecp2-/y mice, and probably Rett patients, originate in part from a deficiency in noradrenergic and serotonergic modulation of the medullary respiratory network.

Animals↗

PubMed2005

Do children with Williams syndrome fail to process visual configural information?

Configural visual abilities in thirteen children with Williams syndrome (WS) compared to 13 children matched on mental age and 13 children matched on chronological age. Configural abilities were tested through four tasks (1) Silhouette (2) Fragmented (3) Mooney and (4) overlapping figures. In the first three tasks, it was necessary to take into account the global information, as the identification of the figures could not be established through a local analysis. In the fourth task, the global configuration of the display had to be ignored. Configural skills seem appropriate in the WS population. A possible dissociation between perceptual and visuo-constructive configural competences is discussed.

Child↗

PubMed2005

Global and local music perception in children with Williams syndrome.

Musical processing can be decomposed into the appreciation of global and local elements. This global/local dissociation was investigated with the processing of contour-violated and interval-violated melodies. Performance of a group of 16 children with Williams syndrome and a group of 16 control children were compared in a same-different task. Control participants were more accurate in detecting differences in the contour-violated than in the interval-violated condition while Williams syndrome individuals performed equally well in both conditions. This finding suggests that global precedence may occur at an early perceptual stage in normally developing children. In contrast, no such global precedence is observed in the Williams syndrome population. These data are discussed in the context of atypical cognitive profiles of individuals with Williams syndrome.

Acoustic Stimulation↗

PubMed2005

Early brain lesions and face-processing development.

Studies of functional plasticity after pre- or perinatal brain damage can tell us whether the neural substrate normally involved in the development of a given ability is specific and, if so, when it becomes functionally specified and unique. Development of face processing was investigated in 5- to 17-year-old children who had a unilateral brain injury in the pre-, peri-, or postnatal period. In Studies 1 and 2, patients with a posterior injury involving the temporal regions exhibited a face-processing deficit that was independent of their age at test time. Even though differences were observed between the two hemispheres in face processing during infancy as well as in adults in cases of normal development, no clear differences between right and left injury were observed here in face-processing deficit. Poor postlesional face-processing plasticity seems to contrast with results of several studies on speech development after early unilateral injury. If the difference in the time window for postlesional plasticity between these two areas of competency is confirmed, it would suggest that the two kinds of abilities rely on neural cells which are sensitive to different plasticity factors.

Adolescent↗

PubMed2003

Topiramate: efficacy and tolerability in children according to epilepsy syndromes.

To evaluate the efficacy and tolerability of topiramate (TPM) as add-on therapy in children less than 12 years of age with refractory epilepsy, according to epilepsy syndromes, we conducted an open, prospective, pragmatic and multicenter study in France. Efficacy was assessed, especially according to epilepsy syndromes, as well as tolerability. We included 207 children (41 of whom were less than 4 years of age). TPM was effective (responders with >50% decrease in seizure frequency) in 50% of 128 patients with partial epilepsy, and in 44% of 79 patients with generalized epilepsy. In case of generalized epilepsy, responders more frequently had generalized symptomatic epilepsy, severe myoclonic epilepsy and myoclono-astatic epilepsy, whereas response rate was mild in both infantile spasms and Lennox-Gastaut syndrome (LGS). Improvement was well maintained in all patients during the treatment period (median 5.6 months). Seizure frequency/severity increased (worsening) in 13% of patients with partial epilepsy and 17% with generalized epilepsy (particularly in those with infantile spasms), and resulted in withdrawal of TPM for 8%. The most frequently reported adverse events were moderate neurobehavioral and gastrointestinal disorders. Adverse events led to withdrawal of TPM from 13.5% of patients. Children less than 4 years of age had particularly good tolerability. Results confirm that TPM is effective and well tolerated in children under 12 years of age in a broad range of epilepsy syndromes, including refractory partial epilepsy, and symptomatic and myoclonic generalized epilepsy. Use of TPM should be considered in children under 4 years of age, and slow and progressive titration is important.

Anticonvulsants↗

PubMed2002

Polymorphisms in the C-terminal domain of MECP2 in mentally handicapped boys: implications for genetic counselling.

Numerous recent reports have proposed that mutations in the C-terminal domain of the MECP2 gene could be a frequent cause of mental retardation in males. We have identified two mutations in this particular domain (S359P and E397K) in two boys who were screened for MECP2 mutations in a series of 23 mentally handicapped boys fitting the clinical description of the previously reported cases. A detailed familial study based on three generations shows that the first mutation (S359P) was also inherited by a healthy cousin thus ruling out its involvement in the etiology of the phenotype of this patient. The second mutation (E397K) was also found in normal individuals. These findings clearly call for a careful consideration of the pathogenicity of the MECP2 mutations identified in sporadic male cases before genetic counselling or prenatal diagnosis is proposed to the corresponding families.

Amino Acid Substitution↗