Novel mutations of TCOF1 gene in European patients with treacher Collins syndrome

Background: Treacher Collins syndrome (TCS) is one of the most severe autosomal dominant congenital disorders of craniofacial development and shows variable phenotypic expression. TCS is extremely rare, occurring with an incidence of 1 in 50.000 live births. The TCS distinguishing characteristics are represented by down slanting palpebral fissures, coloboma of the eyelid, micrognathia, microtia and other deformity of the ears, hypoplastic zygomatic arches, and macrostomia. Conductive hearing loss and cleft palate are often present. TCS results from mutations in the TCOF1 gene located on chromosome 5, which encodes a serine/alanine-rich nucleolar phosphoprotein called Treacle. However, alterations in the TCOF1 gene have been implicated in only 81-93% of TCS cases. Methods: In this study, the entire coding regions of the TCOF1 gene, including newly described exons 6A and 16A, were sequenced in 46 unrelated subjects suspected of TCS clinical indication. Results: Fifteen mutations were reported, including twelve novel and three already described in 14 sporadic patients and in 3 familial cases. Moreover, seven novel polymorphisms were also described. Most of the mutations characterised were microdeletions spanning one or more nucleotides, in addition to an insertion of one nucleotide in exon 18 and a stop mutation. The deletions and the insertion described cause a premature termination of translation, resulting in a truncated protein. Conclusion: This study confirms that almost all the TCOF1 pathogenic mutations fall in the coding region and lead to an aberrant protein

Obstructive sleep apnea in Treacher Collins syndrome

The aim of the present study was to investigate the prevalence of obstructive sleep apnea syndrome (OSAS) among the Norwegian population with Treacher Collins syndrome (TCS). A secondary aim was to establish whether TCS phenotype severity is associated with OSAS severity. A prospective case study design was used. Individuals who were 5 years old and above with a known diagnosis of TCS in Norway were invited to participate in a study. The study included genetic testing, medical and dental examinations and polysomnography. All participants demonstrated disturbed respiration during sleep; 18/19 met the diagnostic criteria for OSAS. Subjectively evaluated snoring was not a reliable predictor of OSAS. We found no significant association between TCS phenotype severity and the severity of OSAS. OSAS is common in TCS, but there is no association with the phenotype severity. Individuals diagnosed with TCS must undergo sleep studies to identify the presence of OSAS

A reality check(list) for digital methods

Digital Methods can be defined as the repurposing of the inscriptions generated by digital media for the study of collective phenomena. The strength of these methods comes from their capacity to take advantage of the data and computational capacities of online platforms; their weakness comes from the difficulty to separate the phenomena that they investigate from the features of the media in which they manifest (‘the medium is the message’, according to McLuhan’s 1964 dictum). In this article, we discuss various methodological difficulties deriving from the lack of separation between medium and message and propose eight practical precautions to deal with it

Evaluating adherence to the Dutch guideline for diagnosis, treatment and follow-up of laryngeal carcinomas

Contains fulltext : 47451.pdf (publisher's version ) (Closed access)BACKGROUND AND PURPOSE: An evidence-based clinical practice guideline for laryngeal carcinomas was introduced in the Netherlands late 1999. The objective of this guideline was to ensure uniformity in the diagnosis, treatment, and follow-up. We retrospectively evaluated whether clinical practice changed according to the recommendations of this guideline and whether it succeeded in its aim. MATERIAL AND METHODS: In five out of eight Dutch university hospitals, chart data of 459 patients treated before the guideline introduction were compared to data of 363 patients treated after the guideline introduction. RESULTS: Patient and tumour characteristics were comparable among both groups. In general, the guideline recommendations were properly complied with. The patients treated before the guideline introduction were actually also for a large part already treated according to the guideline's recommendations. After its introduction, several changes according to the guideline were observed: increased rates of reassessment of biopsy samples taken in local hospitals, psychological screening (although still only performed in 10.5% of patients), application of accelerated radiotherapy schedules, clinical trial treatments, function-preserving treatments, and decreased rates of total laryngectomy, and annual chest X-rays during follow-up. CONCLUSIONS: Although a causal relationship cannot be established in this kind of observational studies, several positive changes were observed after the introduction of the guideline, and therefore the guideline seems to have contributed to more uniformity. The largest changes were seen for the guideline recommendations based on the highest levels of evidence

Undertreatment of tracheal carcinoma: multidisciplinary audit of epidemiologic data.

Contains fulltext : 81051.pdf (publisher's version ) (Closed access)National epidemiologic data were examined to determine the eligibility for curative therapy in tracheal carcinoma. An expert audit of primary tracheal carcinomas registered from 2000 to 2005 with the Netherlands Cancer Registry (NCR) included blinded patient data and radiographic review to assess diagnosis and resectability. Actual treatment was compared with the opinions of a multidisciplinary panel (Radboud panel) and a second reviewer. Of 101 NCR-registered primary tracheal carcinomas, the Radboud panel diagnosis was metastatic disease or local extension of adjacent tumors in 34. Seventeen cases were excluded for missing data. In 50 cases confirmed by panel and a second reviewer, actual treatment consisted of surgery in 12 (24%), radiotherapy in 29 (58%), endobronchial treatment in 6 (12%), and observation in 3 (6%). Both panel and second reviewer identified 16 additional surgical candidates, a total of 28 (56%) of 50. Treatment recommendations of panel and second reviewer disagreed in four cases (8%). One-third of NCR-registered primary tracheal carcinomas were misclassified nontracheal primary tumors involving the trachea. A majority of cases meeting audit criteria for diagnosis and surgical resection was treated with other modalities. Interreviewer disagreement was small. The audit of a national cancer registry suggests that incorrect diagnosis and undertreatment are common in rare airway tumors

Citizens, Consumers and Animals: What Role do Experts Assign to Public Values in Establishing Animal Welfare Standards?

The public can influence animal welfare law and regulation. However what constitutes \u27the public\u27 is not a straightforward matter. A variety of different publics have an interest in animal use and this has implications for the governance of animal welfare. This article presents an ethnographic content analysis of how the concept of a public is mobilized in animal welfare journals from 2003 to 2012. The study was undertaken to explore how experts in the discipline define and regard the role of the public in determining animal welfare standards. Analysis indicates that experts in animal welfare constitute different types of citizen and consumer publics around specific types of animal use, framed by different theories of value. These results suggest a need for greater clarity about the roles and responsibilities of experts and publics in animal welfare reform processes. Clearly citizens and consumers can both contribute to promoting higher welfare standards, but an over-reliance on market mechanisms and consumer behaviour to assign value is beset by moral hazards, foremost being the risk of disarticulating the concept of animal welfare from the public good