Auriculo-condylar syndrome: mapping of a first locus and evidence for genetic heterogeneity

Auriculo-condylar syndrome (ACS), an autosomal dominant disorder of first and second pharyngeal arches, is characterized by malformed ears (`question mark ears`), prominent cheeks, microstomia, abnormal temporomandibular joint, and mandibular condyle hypoplasia. Penetrance seems to be complete, but there is high inter-and intra-familial phenotypic variation, with no evidence of genetic heterogeneity. We herein describe a new multigeneration family with 11 affected individuals (F1), in whom we confirm intra-familial clinical variability. Facial asymmetry, a clinical feature not highlighted in other ACS reports, was highly prevalent among the patients reported here. The gene responsible for ACS is still unknown and its identification will certainly contribute to the understanding of human craniofacial development. No chromosomal rearrangements have been associated with ACS, thus mapping and positional cloning is the best approach to identify this disease gene. To map the ACS gene, we conducted linkage analysis in two large ACS families, F1 and F2 (F2; reported elsewhere). Through segregation analysis, we first excluded three known loci associated with disorders of first and second pharyngeal arches (Treacher Collins syndrome, oculo-auriculo-vertebral spectrum, and Townes-Brocks syndrome). Next, we performed a wide genome search and we observed evidence of linkage to 1p21.1-q23.3 in F2 (LOD max 3.01 at theta = 0). Interestingly, this locus was not linked to the phenotype segregating in F1. Therefore, our results led to the mapping of a first locus of ACS (ACS1) and also showed evidence for genetic heterogeneity, suggesting that there are at least two loci responsible for this phenotype.

Mandibulofacial Dysostosis, Severe Lower Eyelid Coloboma, Cleft Palate, and Alopecia: A New Distinct Form of Mandibulofacial Dysostosis or a Severe Form of Johnson-McMillin Syndrome?

We describe a patient with a phenotype characterized by mandibulofacial dysostosis with severe lower eyelid coloboma, cleft palate, abnormal ears, alopecia, delayed eruption and crowded teeth, and sensorioneural hearing loss. The karyotype and the screening for mutations in the coding region of TCOF1 gene were normal. The clinical signs of our case overlap the new mandibulofacial dysostosis described by Stevenson et al. [2007] and the case with Johnson-McMillin syndrome described by Cushman et al. [2005]. The similar clinical signs, mainly, the severe facial involvement observed in these cases suggest that they can represent a new distinct form of mandibulofacial dysostosis or the end of the spectrum of Johnson McMillin syndrome. (C) 2010 Wiley-Liss, Inc.

Mandibulofacial Syndrome With Growth and Mental Retardation, Microcephaly, Ear Anomalies With Skin Tags, and Cleft Palate in a Mother and Her Son: Autosomal Dominant or X-Linked Syndrome?

We report on a Brazilian mother and her son affected with mandibulofacial dysostosis, growth and mental retardation, microcephaly, first branchial arch anomalies, and cleft palate. To date only three males and one female, all sporadic cases, with a similar condition have been reported. This article describes the first familial case with this rare condition indicating autosomal dominant or X-linked inheritance. (C) 2009 Wiley-Liss, Inc.

Tissue specific roles for the Ribosome Biogenesis Factor Wdr43 in zebrafish development

During vertebrate craniofacial development, neural crest cells (NCCs) contribute to most of the craniofacial pharyngeal skeleton. Defects in NCC specification, migration and differentiation resulting in malformations in the craniofacial complex are associated with human craniofacial disorders including Treacher-Collins Syndrome, caused by mutations in TCOF1. It has been hypothesized that perturbed ribosome biogenesis and resulting p53 mediated neuroepithelial apoptosis results in NCC hypoplasia in mouse Tcof1 mutants. However, the underlying mechanisms linking ribosome biogenesis and NCC development remain poorly understood. Here we report a new zebrafish mutant, fantome (fan), which harbors a point mutation and predicted premature stop codon in zebrafish wdr43, the ortholog to yeast UTP5. Although wdr43 mRNA is widely expressed during early zebrafish development, and its deficiency triggers early neural, eye, heart and pharyngeal arch defects, later defects appear fairly restricted to NCC derived craniofacial cartilages. Here we show that the C-terminus of Wdr43, which is absent in fan mutant protein, is both necessary and sufficient to mediate its nucleolar localization and protein interactions in metazoans. We demonstrate that Wdr43 functions in ribosome biogenesis, and that defects observed in fan mutants are mediated by a p53 dependent pathway. Finally, we show that proper localization of a variety of nucleolar proteins, including TCOF1, is dependent on that of WDR43. Together, our findings provide new insight into roles for Wdr43 in development, ribosome biogenesis, and also ribosomopathy-induced craniofacial phenotypes including Treacher-Collins Syndrome.

Haploinsufficiency of a Spliceosomal GTPase Encoded by EFTUD2 Causes Mandibulofacial Dysostosis with Microcephaly

Mandibulofacial dysostosis with microcephaly (MFDM) is a rare sporadic syndrome comprising craniofacial malformations, microcephaly, developmental delay, and a recognizable dysmorphic appearance. Major sequelae, including choanal atresia, sensorineural hearing loss, and cleft palate, each occur in a significant proportion of affected individuals. We present detailed clinical findings in 12 unrelated individuals with MFDM; these 12 individuals compose the largest reported cohort to date. To define the etiology of MFDM, we employed whole-exome sequencing of four unrelated affected individuals and identified heterozygous mutations or deletions of EFTUD2 in all four. Validation studies of eight additional individuals with MFDM demonstrated causative EFTUD2 mutations in all affected individuals tested. A range of EPTUD2-mutation types, including null alleles and frameshifts, is seen in MFDM, consistent with haploinsufficiency; segregation is de novo in all cases assessed to date. U5-116kD, the protein encoded by EFTUD2, is a highly conserved spliceosomal GTPase with a central regulatory role in catalytic splicing and post-splicing-complex disassembly. MFDM is the fast multiple-malformation syndrome attributed to a defect of the major spliceosome. Our findings significantly extend the range of reported spliceosomal phenotypes in humans and pave the way for further investigation in related conditions such as Treacher Collins syndrome.

Virtually real : Suzanne Collins's the Hunger Games Trilogy

The Hunger Games trilogy by Suzanne Cololins deals with a dystopian future society in which a punitive ruling elite provide 'entertainment' for the masses in the form of mediatised 'games' featuring young people who must fight to kill one another until there is only one winner. The purpose of these games is to remind the populace of the power of the government and its ability to dispose of any who dare defy it. In acknowledging violent 'games' as virtual entertainments which can be used to political effect, Collins suggests that they possess a disturbing capacity to undermine ethical perspective on the human,the humane and the real. Drawing on Baudrillard's ideas about simulation and simulacra as well as Elaine Scarry's and Susan Sontag's concerns for media representations of the body in pain, this paper discusses the ways in which the texts highlight the dangers of virtual modes while also risking perpetuating their entertainment value.

Implementación de HyD [Hidroxicolecalciferol (25-OH-D3)] en la dieta de pollos de engorde como profilaxis de osteopatías, enfatizando en el sindrome del hueso negro, Granja Trinidad-1, Tip Top industrial

El objetivo del experimento fue evaluar el efecto del Hidroxicolecalciferol [HyD (25 –OH- D3)] en pollos de engorde, atraves de porcentajes de ceniza, calcio, fosforo y diagnostico de síndrome de hueso negro, se evaluaron dos tratamientos ( HyD y Testigo) con seis repeticiones para cada uno en dos tiempos a los 21 y 35 días de edad en análisis de ceniza, calcio y fosforo para lo cual se extrajo una tibia por pollo, dichos análisis resultaron con diferencias no significativas en ambas edades, las evaluaciones dieron como resultado que de los 21 día a los 35 días disminuyen su valor, ceniza baja de 43.8% a 36.8% en el testigo y de 42.4% a 37.7% en HyD, calcio de 15.6% a 13.4% para el testigo y de 16% a 14.5% para HyD de igual manera para los porcentaje de fosforo de 21 a 35 días con 7.6% a 6.5% para testigo y 7.5% a 6.7% para HyD. A los 35 días los resultados son mayores en el grupo HyD, 37.7% HyD,36.8% testigo en ceniza, calcio 14.5% HyD, testigo 13.4% y fosforo 6.7% HyD , 6.5% para testigo, las diferencias de 21 a 35 días son notorias y conservan la parte proporcional en que los porcentajes estan en ceniza calcio y fosforo, pero estas disminuyen para una misma variable de los 21 días de edad a los 35, sin encontrar diferencia significativas. A los 35 días se realizo análisis de síndrome de hueso negro con un total de 22 repeticiones por tratamiento, la extracción de dicha muestra (tibia) se realizo en planta de proceso, el análisis determino diferencias entre las aves muestreadas dando los mejores resultados aquellas que fueron alimentadas con Hidroxicolecalciferol [HyD (25 –OH- D3)], se observo en los resultados que en el grupo con HyD alcanzo un 91% de individuos sanos superando significativamente al testigo que solo llego a un 77% de individuos sanos, empleando un grado de libertad y 0.05 de significancia, lo que indica diminución de la presencia del síndrome de hueso negro, producto del HyD, empleando la línea genética Cobb 500, y alimentando los pollos del día cero al día 21 con diferencias de tratamiento e igual alimento del día 22 al día 35.

LC teknika desberdinen erabilera Sindrome metabolikoaren aurkako terapian erabiltzen diren farmakoen determinaziorako

330 p.

Edoskitzea, opioideoen ondoriozko abstinentzia sindrome neonatalaren tratamendu eraginkorra?

[EUS]Helburuak: Berrikuspen bibliografiko honen helburu orokorra edoskitzea opioideekiko abstinentzia sindrome neonatalaren sintomak arintzeko eraginkorra den aztertzea izango da, eta baita honek tratamendu farmakologikoaren beharra gutxitzen duen. Bestalde, metadona hartzen duten emakume hauen esneko metadona kontzentrazioa nolakoa den eta esne honen bitartez jaioberriari heltzen zaion kantitatea nolakoa den identifikatu nahi da. Metodologia: Artikuluen bilaketa egiteko, datu base desberdinak erabili dira, baina erabilitako azken 8 artikuluak Pubmed eta Ovid-sp-ekoak dira. Artikulu guztiak bat izan ezik, ingelesezkoak dira, gaztelaniaz aurkitutako artikulu kantitate eskasa dela eta. “Edoskitzea” , “abstinentzia sindrome neonatala” eta “metadona terapia" terminoak erabili dira bilaketa prozesuan. Ondorioak: Edoskitzea opioideekiko abstinentzia sindrome neonatala jasaten duten jaioberrientzat gomendagarria dela esan daiteke, ikerketa hauen arabera, abstinentziaren sintomak eta tratamendu farmakologikoaren beharra gutxitzen baititu. Gainera, esneko metadona kontzentrazioa eta jaioberriari honen bitartez heltzen zaion kantitatea oso txikiak dira. Hala ere, lanak limitazioa garrantzitsu bat du, ikerketetako laginak txikiak izatea.

Collins Weir in River Wyre 1935

Collins Weir in River Wyre, North West England, UK. Photo taken on the 7th of September 1935. This photo is part of a Photo Album that includes pictures from 1935 to 1954.

Wilkie Collins

Pykett, L. (2005). Wilkie Collins. Authors in Context Series. Oxford: Oxford University Press. RAE2008