Loss-of-Function Mutations in LRRC6, a Gene Essential for Proper Axonemal Assembly of Inner and Outer Dynein Arms, Cause Primary Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is a group of autosomal-recessive disorders resulting from cilia and sperm-flagella defects, which lead to respiratory infections and male infertility. Most implicated genes encode structural proteins that participate in the composition of axonemal components, such as dynein arms (DAs), that are essential for ciliary and flagellar movements; they explain the pathology in fewer than half of the affected individuals. We undertook this study to further understand the pathogenesis of PCD due to the absence of both DAs. We identified, via homozygosity mapping, an early frameshift in LRRC6, a gene that encodes a leucine-rich-repeat (LRR)-containing protein. Subsequent analyses of this gene mainly expressed in testis and respiratory cells identified biallelic mutations in several independent individuals. The situs inversus observed in two of them supports a key role for LRRC6 in embryonic nodal cilia. Study of native LRRC6 in airway epithelial cells revealed that it localizes to the cytoplasm and within cilia, whereas it is absent from cells with loss-of-function mutations, in which DA protein markers are also missing. These results are consistent with the transmission-electron-microscopy data showing the absence of both DAs in cilia or flagella from individuals with LRRC6 mutations. In spite of structural and functional similarities between LRRC6 and DNAAF1, another LRR-containing protein involved in the same PCD phenotype, the two proteins are not redundant. The evolutionarily conserved LRRC6, therefore, emerges as an additional player in DA assembly, a process that is essential for proper axoneme building and that appears to be much more complex than was previously thought

Un aperçu de la formation et des pratiques professionnelles en Europe sur l'accompagnement des compétences en communication des jeunes présentant un trouble du développement intellectuel

peer reviewedLes difficultés de communication des personnes présentant un trouble du développement intellectuel engendrent un risque d’exclusion tant les compétences communicationnelles sont cruciales pour les apprentissages, l’inclusion sociale et, l’autodétermination. Quelle est la situation actuelle en Europe dans ce domaine ? C’est ce qu’a tenté d’identifier l’étude menée dans le cadre du projet ERASMUS+ COM-IN en interrogeant via un questionnaire les professionnels travaillant avec des jeunes européens ayant un TDI. Des données préliminaires de cette étude sont présentées.COM-IN Améliorer les compétences émotionnelles des jeunes avec un trouble du développement intellectuel pour favoriser leur inclusion4. Quality educatio

Carotenoid profiling of tropical root crop chemotypes from Vanuatu, South Pacific

International audienceTropical root and tuber crops are staple foods in developing countries where they are the main source of carbohydrates and a potential source of secondary metabolites such as carotenoids. Enhancing carotenoid content has considerable potential for improving human nutrition in these areas. Except for cassava and sweet potato, carotenoid content has not been evaluated in large germplasm collections. We describe a simple HPLC-DAD-based protocol for the reliable characterization of carotenoids in root crops. Less than 5% variation in carotenoid content was found among samples collected from tubers of the same plant or from clones of the same genotype. Carotenoids were evaluated in 153 accessions representing 10 different species. Each species had a specific profile of carotenoids, and accessions of the same species differed greatly in their individual content. The database assembled during this study represents a useful tool for nutritionists and breeders working on biofortification of root crops with carotenoids

Profils métaboliques de plantes tropicales à racines et tubercules du Vanouatou (Mélanésie)

National audienc

Cystic fibrosis carrier frequency and estimated prevalence of the disease in Morocco

International audienceBackground: The epidemiology of cystic fibrosis (CF) is poorly known in North African populations, in particular in Morocco and the CF carrier frequency in the general Moroccan population has never been evaluated. Methods: To estimate the prevalence of CF mutations in Morocco, blood samples from 150 healthy Moroccans were tested for frequent CFTR mutations and the intron 8 polyT variant. Results: Two subjects were heterozygous for F508del and eight others for the (T)5 variant. Conclusion: These findings indicate that the Moroccan population is at risk for CF and CFTR-related disorders. CF prevalence could be in the range of that found in European populations. Wider studies are necessary to identify the clinical pattern and accurately determine the prevalence and molecular basis of CF in Morocco

Increased risk of coronary artery disease in Caucasians with extremely low HDL cholesterol due to mutations in ABCA1, APOA1, and LCAT

Mutations in ABCA1, APOA1, and LCAT reduce HDL cholesterol (HDLc) in humans. However, the prevalence of these mutations and their relative effects on HDLc reduction and risk of coronary artery disease (CAD) are less clear. Here we searched for ABCA1, APOA1, and LCAT mutations in 178 unrelated probands with HDLc = 1 first-degree relative with low HDLc (familial probands) and 89 where familial status of low HDLc is uncertain (unknown probands). Mutations were most frequent in LCAT (15.7%), followed by ABCA1 (9.0%) and APOA1 (4.5%), and were found in 42.7% of familial but only 14.6% of unknown probands (p=2.44 10(-5)). Interestingly, only 16 of 24 (66.7%) mutations assessed in families conferred an average HDLc 40% of familial hypoalphalipoproteinemia in this cohort. Moreover, individuals with mutations and large reductions in HDLc have increased risk of CAD. This article is part of a Special Issue entitled Advances in High Density Lipoprotein Formation and Metabolism: A Tribute to John F. Oram (1945-2010). (C) 2011 Elsevier B.V. All rights reserve

The clinical course of interstitial lung disease in an adult patient with an ABCA3 homozygous complex allele under hydroxychloroquine and a review of the literature.

International audienceThe gene mutations responsible for ABCA3 protein deficiency are involved in respiratory distress of the newborn and much more rarely in adult interstitial lung diseases (ILD). An adult patient homozygous for a complex allele encompassing the p.Ala1027Pro likely pathogenic mutation and the p.Gly974Asp variation was followed for a late-onset and fibrotic ILD. The evolution was marked by progressive clinical and functional degradation despite corticosteroid pulses. The patient, who was first registered on the list for lung transplantation, was improved quickly and persistently for at least 6.5 years with hydroxychloroquine treatment, allowing removal from the transplant list

How communication skills in youth with intellectual developmental disabilities are supported: An overview of the professional training and practices in Europe

peer reviewedIntellectual developmental disorder (IDD) is a neurodevelopmental disorder that includes a disability in intellectual functioning and adaptative functioning. Most persons with IDD experience communication difficulties and, the more they struggle with communication difficulties, the more they experience difficulties in self-determination, social inclusion, and interpersonal relationships. Communication difficulties lead to a risk of exclusion since communication skills are crucial to learning, working, developing relationships, and engaging in different social contexts. Thus, it is essential to support communication to promote the individuals’ social and professional inclusion, and trained professionals are crucial in this support. Yet, the appropriate strategies to support communication are rarely implemented. Specifically, support dedicated to adolescents and young adults is still scarce. In addition, most people consider that supporting the communication needs of people with IDD is the role of specialized professionals such as speech and language therapists. While it is true that their role is central, this is insufficient to ensure continued progress in communicative skills. American Speech-Language-Hearing Association (ASHA) emphasized that supporting communication in people with communication needs requires that their environment expects that they can and will communicate and thus all persons should engage to cooperate in communication. In addition, promoting communication in people with communication needs should be integrated into the daily communication environments, and it requires the knowledge and skills of parents and professionals from a variety of disciplines. The current submission presents preliminary data from a survey conducted within the ERASMUS+COM-IN Project with the aim, before creating training materials, to gather information concerning the communication needs of youth with IDD and the way communication skills are supported by the professionals working with them. The questionnaire included questions concerning professionals’ knowledge and training on communication skills, the way these skills are addressed in their organization, their practices concerning communication skills, how they work with youth families, and questions concerning employment and working conditions. The questionnaire was implemented on the online survey tool, Limesurvey, and it was sent to professionals working with youth with IDD in Belgium, Greece, France, Finland, and Spain. We expect to identify which professionals are involved in supporting communication skills and which are their training and current professional practices, but also those of the professionals who declare not being involved in supporting communication (ex: do they spontaneously adopt strategies to facilitate communication with youth with IDD?), and to show that working conditions are related to professionals’ training and practices.COM-IN Améliorer les compétences émotionnelles des jeunes avec un trouble du développement intellectuel pour favoriser leur inclusion4. Quality educatio

Notable contribution of large CFTR gene rearrangements to the diagnosis of cystic fibrosis in fetuses with bowel anomalies

Grade III fetal bowel hyperechogenicity and/or loop dilatation observed at the second trimester of pregnancy can be due to several disease conditions, including cystic fibrosis (CF). Screening for frequent CF mutations is performed as a first step and, in certain situations, such as when a frequent CF mutation is found in the fetus, the increased risk of CF justifies an in-depth study of the second allele. To determine the contribution of large CFTR gene rearrangements in such cases, detected using a semiquantitative fluorescent multiplex PCR (QFM-PCR) assay, we collated data on 669 referrals related to suspicion of CF in fetuses from 1998 to 2009. Deletions were found in 5/70 cases in which QFM-PCR was applied, dele19, dele22_23, dele2_6b, dele14b_15 and dele6a_6b, of which the last three remain undescribed. In 3/5 cases, hyperechogenicity was associated with dilatation and/or gallbladder anomalies. Of the total cases of CF recognized in the subgroup of first-hand referrals, deletions represent 16.7% of CF alleles. Our study thus strengthens the need to consider large CFTR gene rearrangements in the diagnosis strategy of fetal bowel anomalies, in particular in the presence of multiple anomalies