Defects in the IFT-B component IFT172 cause Jeune and Mainzer-Saldino syndromes in humans

Intraflagellar transport (IFT) depends on two evolutionarily conserved modules, subcomplexes A (IFT-A) and B (IFT-B), to drive ciliary assembly and maintenance. All six IFT-A components and their motor protein, DYNC2H1, have been linked to human skeletal ciliopathies, including asphyxiating thoracic dystrophy (ATD; also known as Jeune syndrome), Sensenbrenner syndrome, and Mainzer-Saldino syndrome (MZSDS). Conversely, the 14 subunits in the IFT-B module, with the exception of IFT80, have unknown roles in human disease. To identify additional IFT-B components defective in ciliopathies, we independently performed different mutation analyses: candidate-based sequencing of all IFT-B-encoding genes in 1,467 individuals with a nephronophthisis-related ciliopathy or whole-exome resequencing in 63 individuals with ATD. We thereby detected biallelic mutations in the IFT-B-encoding gene IFT172 in 12 families. All affected individuals displayed abnormalities of the thorax and/or long bones, as well as renal, hepatic, or retinal involvement, consistent with the diagnosis of ATD or MZSDS. Additionally, cerebellar aplasia or hypoplasia characteristic of Joubert syndrome was present in 2 out of 12 families. Fibroblasts from affected individuals showed disturbed ciliary composition, suggesting alteration of ciliary transport and signaling. Knockdown of ift172 in zebrafish recapitulated the human phenotype and demonstrated a genetic interaction between ift172 and ift80. In summary, we have identified defects in IFT172 as a cause of complex ATD and MZSDS. Our findings link the group of skeletal ciliopathies to an additional IFT-B component, IFT172, similar to what has been shown for IFT-A.

Estudio de Protictitherium crassum del Cerro de los Batallones (Torrejón de Velasco, Madrid): aportación a la filogenia y evolución de la familia hyaenidae

En esta tesis doctoral se aborda el estudio sistemático y paleobiológico de los fósiles del hiénido Protictitherium crassum FILHOL, 1883 del sistema de yacimientos miocenos del Cerro de los Batallones (Torrejón de Velasco, Madrid, España). La abundancia, representatividad y el excepcional estado de conservación de los restos fósiles hallados en los yacimientos del Cerro de los Batallones, de edad Vallesiense (MN 10), han permitido contar con una excelente colección de material fósil para un estudio morfológico, sistemático, filogenético y paleobiológico detallado...

Galerie du Musée Napoléon /

"Dédiée a S. M. l'Empereur Napoloéon I.er."

Eaux minérales des pyrénées : recherches comprenant l'étude de l'action thérapeutique, la constitution chimique de ces eaux ... /

Mode of access: Internet.

Musée Royal de France, ou collection gravée des chefs-d'oeuvre de peinture et sculpture dont ils'est enrichi depuis la restauration avec un texte rédig ́par M.A. Jal.

Mode of access: Internet.