A rare large mutation involving two exons of the SP-B gene in an infant with severe respiratory distress

Hereditary surfactant protein-B (SP-B) deficiency is a rare autosomal recessive disease of newborn infants causing severe respiratory failure and death within the first year of life. The most common cause of SP-B deficiency is a frameshift mutation in exon 4 (121ins2) in the gene encoding SP-B. We report a term infant with unremitting respiratory distress who was unresponsive to all treatment modalities. The parents were consanguineous and a term sibling of the infant had died due to respiratory failure without a certain diagnosis. In the first step of the diagnostic work-up, common genetic mutations for SP-B, surfactant protein C and ATP-binding cassette s3 were absent, however sequencing of SP-B gene revealed a large homozygous genomic deletion covering exon 8 and 9. In this case report, we aimed to emphasize further genetic evaluation in all cases suggestive of surfactant dysfunction, even if common mutations are absent

Survival of an Infant with Homozygous Surfactant Protein C (SFTPC) Mutation

Lung diseases caused by surfactant protein C (SFTPC) mutations are inherited as autosomal traits with variable penetrance and severity or as sporadic disease caused by a de novo mutation on one allele. Here, we report the case of a child surviving with a homozygous surfactant protein C mutation after aggressive clinical management unlike his six siblings who died in infancy. This presentation raises the suspicion of an autosomal recessive inheritence that is discussed in this report. Pediatr Pulmonol. 2014; 49:E112-E115. (c) 2013 Wiley Periodicals, Inc

Temperature-sensitive auditory neuropathy associated with an otoferlin mutation: Deafening fever!

International audienceTransient deafness associated with an increase in core body temperature is a rare and puzzling disorder. Temperature-dependent deafness has been previously observed in patients suffering from auditory neuropathy. Auditory neuropathy is a clinical entity of sensorineural deafness characterized by absent auditory brainstem response and normal otoacoustic emissions. Mutations in OTOF, which encodes otoferlin, have been previously reported to cause DFNB9, a non-syndromic form of deafness characterized by severe to profound prelingual hearing impairment and auditory neuropathy.Here we report a novel mutation in OTOF gene in a large family affected by temperature-dependent auditory neuropathy. Three siblings aged 10, 9 and 7 years from a consanguineous family were found to be affected by severe or profound hearing impairment that was only present when they were febrile. The non-febrile patients had only mild if any hearing impairment. Electrophysiological tests revealed auditory neuropathy. Mapping with microsatellite markers revealed a compatible linkage in the DFNB9/OTOF region in the family, prompting us to run a molecular analysis of the 48 exons and of the OTOF intron–exon boundaries. This study revealed a novel mutation p.Glu1804del in exon 44 of OTOF. The mutation was found to be homozygous in the three patients and segregated with the hearing impairment within the family. The deletion affects an amino acid that is conserved in mammalian otoferlin sequences and located in the calcium-binding domain C2F of the protein

New surfactant protein C gene mutations associated with diffuse lung disease

International audienceMutations in the surfactant protein C gene () have been recently associated with the development of diffuse lung disease, particularly sporadic and familial interstitial lung disease (ILD). We have investigated the prevalence and the spectrum of mutations in a large cohort of infants and children with diffuse lung disease and suspected with surfactant dysfunction. One hundred twenty-one children were first screened for the common mutation, p.Ile73Thr (I73T). Ten unrelated patients were shown to carry this mutation. The I73T mutation was inherited in 6 cases, and appeared in 4. The 111 patients without the I73T mutation were screened for the entire coding sequence of . Of these, eight (seven unrelated) subjects were shown to carry a novel mutant allele of . All these seven new mutations are located in the BRICHOS domain except the p.Val39Ala (V39A) mutation, which is in the surfactant protein C (SP-C) mature peptide. Our results confirm that mutations are a frequent cause of diffuse lung disease, and that I73T is the most frequent mutation associated with diffuse lung disease

Heterogeneity of lung disease associated with NK2 homeobox 1 mutations

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Dynamiques et modalités du peuplement dans la vallée de la Loire, entre Orléans et Saint-Nazaire, de La Tène moyenne à la fin du règne d’Auguste

International audienceLoire constitutes, in its western part, a major element in the structuring of the landscape and the territories that it crosses in historical periods. This observation, which can be applied to the Iron Age according to the texts of Strabo and Caesar in particular, has only really started to be documented by archeology in recent years. The aim of this contribution is therefore to bring together largely unpublished documentation in order to provide information on three main questions: Development and management of the watercourse (bridges, fords, banks, wrecks) ; The status and organization of sites related to the Loire, in a 50 km wide strip; Cultural entities crossed by the river. Bringing together the results of numerous preventive archaeological interventions and recent academic work, the study demonstrates the Loire's significant attraction for the peoples concerned and its obvious role for long-distance exchanges. It also highlights the preeminent role of the Gallic populations in the human appropriation of the valley.La Loire constitue, dans sa portion occidentale, un élément majeur de la structuration du paysage et des territoires qu’elle traverse aux périodes historiques. Ce constat, que l’on peut appliquer à l’âge du Fer d’après les textes de Strabon et de César notamment, ne commence véritablement à être documenté par l’archéologie que depuis quelques années. Cette contribution a donc pour objectif de rassembler une documentation en grande partie inédite, afin de renseigner trois questions principales : Les aménagements et la gestion du cours d’eau (ponts, gués, berges, épaves) ; Le statut et l’organisation des sites en relation avec la Loire, dans une bande de 50 km de large ; Les entités culturelles traversées par le fleuve. Réunissant les résultats de nombreuses interventions d’archéologie préventives et de travaux universitaires récents, l’étude démontre l’attraction importante de la Loire pour les peuples concernés et son rôle manifeste pour les échanges à longue distance. Elle permet également de mettre en évidence le rôle prééminent des populations gauloises dans l’appropriation humaine du val

Dynamiques et modalités du peuplement dans la vallée de la Loire, entre Orléans et Saint-Nazaire, de La Tène moyenne à la fin du règne d'Auguste

International audienceLoire constitutes, in its western part, a major element in the structuring of the landscape and the territories that it crosses in historical periods. This observation, which can be applied to the Iron Age according to the texts of Strabo and Caesar in particular, has only really started to be documented by archeology in recent years. The aim of this contribution is therefore to bring together largely unpublished documentation in order to provide information on three main questions : Development and management of the watercourse (bridges, fords, banks, wrecks) ; The status and organization of sites related to the Loire, in a 50 km wide strip; Cultural entities crossed by the river. Bringing together the results of numerous preventive archaeological interventions and recent academic work, the study demonstrates the Loire's significant attraction for the peoples concerned and its obvious role for long-distance exchanges. It also highlights the preeminent role of the Gallic populations in the human appropriation of the valley.La Loire constitue, dans sa portion occidentale, un élément majeur de la structuration du paysage et des territoires qu’elle traverse aux périodes historiques. Ce constat, que l’on peut appliquer à l’âge du Fer d’après les textes de Strabon et de César notamment, ne commence véritablement à être documenté par l’archéologie que depuis quelques années. Cette contribution a donc pour objectif de rassembler une documentation en grande partie inédite, afin de renseigner trois questions principales : Les aménagements et la gestion du cours d’eau (ponts, gués, berges, épaves) ; Le statut et l’organisation des sites en relation avec la Loire, dans une bande de 50 km de large ; Les entités culturelles traversées par le fleuve. Réunissant les résultats de nombreuses interventions d’archéologie préventives et de travaux universitaires récents, l’étude démontre l’attraction importante de la Loire pour les peuples concernés et son rôle manifeste pour les échanges à longue distance. Elle permet également de mettre en évidence le rôle prééminent des populations gauloises dans l’appropriation humaine du val

Dynamiques et modalités du peuplement dans la vallée de la Loire, entre Orléans et Saint-Nazaire, de La Tène moyenne à la fin du règne d’Auguste

International audienceLoire constitutes, in its western part, a major element in the structuring of the landscape and the territories that it crosses in historical periods. This observation, which can be applied to the Iron Age according to the texts of Strabo and Caesar in particular, has only really started to be documented by archeology in recent years. The aim of this contribution is therefore to bring together largely unpublished documentation in order to provide information on three main questions: Development and management of the watercourse (bridges, fords, banks, wrecks) ; The status and organization of sites related to the Loire, in a 50 km wide strip; Cultural entities crossed by the river. Bringing together the results of numerous preventive archaeological interventions and recent academic work, the study demonstrates the Loire's significant attraction for the peoples concerned and its obvious role for long-distance exchanges. It also highlights the preeminent role of the Gallic populations in the human appropriation of the valley.La Loire constitue, dans sa portion occidentale, un élément majeur de la structuration du paysage et des territoires qu’elle traverse aux périodes historiques. Ce constat, que l’on peut appliquer à l’âge du Fer d’après les textes de Strabon et de César notamment, ne commence véritablement à être documenté par l’archéologie que depuis quelques années. Cette contribution a donc pour objectif de rassembler une documentation en grande partie inédite, afin de renseigner trois questions principales : Les aménagements et la gestion du cours d’eau (ponts, gués, berges, épaves) ; Le statut et l’organisation des sites en relation avec la Loire, dans une bande de 50 km de large ; Les entités culturelles traversées par le fleuve. Réunissant les résultats de nombreuses interventions d’archéologie préventives et de travaux universitaires récents, l’étude démontre l’attraction importante de la Loire pour les peuples concernés et son rôle manifeste pour les échanges à longue distance. Elle permet également de mettre en évidence le rôle prééminent des populations gauloises dans l’appropriation humaine du val

Screening of SLC26A4, FOXI1 and KCNJ10 genes in unilateral hearing impairment with ipsilateral enlarged vestibular aqueduct

International audienceObjective: To investigate the implication of SLC26A4, FOXI and KCNJ10 genes in unilateral hearing impairment associated with ipsilateral inner ear malformation (Enlargement of the vestibular aqueduct and/or Mondini dysplasia).Methods: We have gathered 25 patients presenting unilateral hearing impairment and ipsilateral enlarged vestibular aqueduct. For each of the patients, we have analyzed SLC26A4, FOXI1 and KCNJ10 genes sequences.Results: The analysis of SLC26A4 revealed only eight heterozygous SLC26A4 sequence variants, three of them being novel (p.Met147Ile, p.Asn538Asn and p.Leu627Arg). None of the patients carried a second mutation on the other allele. Moreover, the SLC26A4 locus was excluded by segregation analysis in two families. No mutations were present in FOXI1 and KCNJ10 genes.Conclusions: Together, these data suggest that SLC26A4, FOXI1 and KCNJ10 are not major determinants in unilateral deafness and enlarged vestibular aqueduct compared with their implication in Pendred syndrome and non-syndromic bilateral enlarged vestibular aqueduct