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Joubert syndrome and related disorders (JSRD) are clinically and genetically heterogeneous ciliopathies sharing a peculiar midbrain–hindbrain malformation known as the ‘molar tooth sign’. To date, 19 causative genes have been identified, all coding for proteins of the primary cilium. There is clinical and genetic overlap with other ciliopathies, in particular with Meckel syndrome (MKS), that is allelic to JSRD at nine distinct loci. We previously identified the INPP5E gene as causative of JSRD in seven families linked to the JBTS1 locus, yet the phenotypic spectrum and prevalence of INPP5E mutations in JSRD and MKS remain largely unknown. To address this issue, we performed INPP5E mutation analysis in 483 probands, including 408 JSRD patients representative of all clinical subgroups and 75 MKS fetuses. We identified 12 different mutations in 17 probands from 11 JSRD families, with an overall 2.7% mutation frequency among JSRD. The most common clinical presentation among mutated families (7/11, 64%) was Joubert syndrome with ocular involvement (either progressive retinopathy and/or colobomas), while the remaining cases had pure JS. Kidney, liver and skeletal involvement were not observed. None of the MKS foetuses carried INPP5E mutations, indicating that the two ciliopathies are not allelic at this locus., peer-reviewed

International audience; Background. - The prevalence of poor reading skills is particularly high among children from low socioeconomic backgrounds, but no longitudinal studies have been conducted so far in France to determine whether poor reading in a socioeconomically challenged population is persistent and warrants preventive action. Design. - One hundred and fifty-four children were divided into three groups according to their reading skills: poor, intermediate and typical readers. They were followed over a period of 2 years. Reading levels, spelling and comprehension were assessed by standardized measurement scales in order to determine reading outcome and predictive variables. Results. - The reading skills in each group progressed at similar rates, but the differences between the three groups remained relatively constant over the 2 years. The gap between good and poor readers actually increased for the poorest readers. Spelling scores followed a similar pattern and remained weak. Comprehension scores followed a different pattern. Most of the initially poor readers with low comprehension scores almost caught up and reached the level of the typical readers. The best predictive variables of reading and spelling outcome were phonological awareness, rapid naming and attention deficit. The strongest predictive variables for comprehension were IQ, lexical level and attention. Conclusions. - Our results confirm the relative stability of reading measurement across time in poor readers from low socioeconomic backgrounds. Their behavior are similar to the classic dyslexic population. The predictive variables are different depending on whether reading or spelling or comprehension is considered. These results provide a clear agenda for preventive literacy action in children with low socioeconomic levels (SES): phonological decoding and oral language skills in early grades, and screening and treatment of attention disorders. (C) 2010 Elsevier Masson SAS. All rights reserved.

International audience; Background. - Reading impairment is the major learning disability in children. While research oil illiteracy has mainly been conducted from a sociological perspective, research on dyslexia has typically been studied from a cognitive-linguistic perspective. Studies that jointly investigate sociological, behavioral and cognitive factors in predicting reading outcome are rare and limited to English-speaking Populations. The goal of the present study was to screen second grade children with reading impairment in French urban elementary schools and to pill down the factors that explain the various facets of reading failure and success. Methods. - A total of 1062 children from 20 different schools in the city of Paris participated in the study. Different aspects of reading were assessed individually for children with a suspected impairment in reading acquisition. Subsequently, 13 1 poor readers and 50 typically developing readers were matched for sex, age, and school. For these children, medical, cognitive, behavioral and individual socioeconomic data were obtained. Group differences were examined and multiple regression analyses were conducted to examine how much variance in reading was explained by the various variables. Results. - The prevalence of poor reading skills in grade 2 was highly influenced by neighborhood socioeconomic status (SES) (ranging from 3.3% in high SES to 20.5% in low SES areas). Among the SES variables, employment of the father was a significant predictor of poor reading. Among the cognitive variables, phonological awareness and rapid naming were the most significant factors. much more than verbal or nonverbal intelligence. Among the behavioral variables, attention was an important factor but not externalized symptoms. Multiple regression analyses showed that reading outcome was best predicted by phonological awareness skills and attention deficits. Conclusion. - The majority of children with reading disability come from low SES areas. As in the English literature, the most robust predictor for reading impairment is phonological awareness, even when SES is taken into account. In addition, attention deficits seemed to aggravate reading impairments for children with weak phonological awareness skills. Successful early prevention should focus oil reinforcing phonological awareness, recoding and attention skills. (C) 2009 Elsevier Masson SAS. All rights reserved.

International audience; Objective. From an original large sample of 1062 7 to 8-year-old children, reading skills were assessed and found to be highly linked with socioeconomic status (SES). The purpose of the present study was to further determine underlying medical, sociocultural, cognitive and behavioural factors explaining the diversity of reading skills and the influence of SES. Method. Individual testing among low-SES children identified 100 poor readers, 50 typical readers and 31 children with intermediate reading scores. All 3 groups underwent a thorough assessment, including a medical evaluation, a full cognitive battery, a structured parental interview and behavioural questionnaire. Logistic regression was used to demonstrate the variables predicting reading score outcome. Results. None of the medical factors studied was statistically related to reading scores. Due to the methodology buffering the impact of SES sociocultural variables, such as parental levels of education, parental occupation, as well as familial income were weak, but statistically significant predictors. The strongest variables were phonological abilities and symptoms of attention disorders. In a final regression model, phonological awareness, level of mother's education and attention explained the differences in reading skills. Conclusions. These results, which are unique in France, are similar to existing data in the literature. They support the need to conceptualize an early screening programme to detect reading difficulties and to promote an intervention based on phonological processing and decoding in low-SES environments. (C) 2008 Elsevier Masson SAS. All Lights reserved.

International audience; Objective. Socioeconomic status (SES) has a known influence on academic achievement. Most studies, however, were conducted in English-speaking countries. Because recent cross-linguistic studies suggest that reading English is much harder to learn than reading other languages, an epidemiological study was conducted in French investigating the impact of socioeconomic background on early reading development. Design. One thousand and twenty second-grade children (476 girls and 544 boys) from 20 different schools participated in the study. Approximately 1/3 of the children lived and were schooled in a high SES area, 1/3 in an intermediate SES area, and one final third in a very low SES area. Assessment of reading, writing and mathematical skills was conducted initially in small groups. Children with suspected learning difficulties were further tested individually. Forty-two children of equivalent age who repeated the first grade received similar individual testing. Results. Average reading scores were in accordance with chronological age, without gender differences. Children from low SES schools had academic performances significantly lower than their peers. Boys exhibited superior arithmetic skills than girls. A significant reading delay was observed in 12.7% of children. The prevalence of poor reading was highly correlated with the area of schooling, varying from 3.3% in the high SES area to 24.2% in low SES area. Conclusion. The high rate of children from our sample with a significant delay in reading depended on general socioeconomic environment. An understanding of the origin of such differences is mandatory for defining and coordinating preventive actions and appropriate interventions. (C) 2008 Elsevier Masson SAS. All rights reserved.

Neuronal ceroid lipofuscinoses represent a heterogeneous group of early onset neurodegenerative disorders that are characterized by progressive cognitive and motor function decline, visual loss, and epilepsy. The age of onset has been historically used for the phenotypic classification of this group of disorders, but their molecular genetic delineation has now enabled a better characterization, demonstrating significant genetic heterogeneity even among individuals with a similar phenotype. The rare Congenital Neuronal Ceroid Lipofuscinosis (CLN10) caused by mutations in the CTSD gene encoding for cathepsin D is associated with a dramatic presentation with onset before or around birth. We report on a female born to consanguineous parents who presented at birth with severe neonatal encephalopathy with massive cerebral and cerebellar shrinking on magnetic resonance imaging. Whole exome sequencing with targeted bioinformatic analysis of a panel of genes associated with prenatal/perinatal onset of neurodegenerative disease was performed and revealed the presence of a novel homozygous in-frame deletion in CTSD. Additional functional studies further confirmed the pathogenic character of this variant and established the diagnosis of CLN10 in the patient.