3,120 research outputs found
LAC, LEETS Chairs, Hodges, and Collins
No full text(l to r) Stephen Cunetto, Julia Hodges, Frances Coleman, June Garner, Tim Collins, Amanda Clay Powers, and Pat Matthes pose for a photograph on Friday
A few poems on Hawaii, China, and America /
No full textIllustrated cover.On cover: Varnum D. Collins, 2155 L St. N.W., Washington, D.C.Mode of access: Internet.Presentation copy to his son, Varnum Lansing Collins (Princeton Class of 1872), signed by the author
Transmitted deletions of medial 5p and learning difficulties; Does the cadherin cluster only become penetrant when flanking genes are deleted?
No full textThe central portion of the short arm of chromosome 5 is unusual in that large, cytogenetically visible interstitial deletions segregate in families with and without phenotypic consequences. Here we present a family in which a transmitted interstitial deletion of 5p13.3 to 5p14.3 co-segregated with learning and/or behavioral difficulties in six family members. Facial dysmorphism was not striking but a father and daughter both had lacrimal fistulae. The deletion was 12.23?Mb in size (chr5:20,352,535–32,825,775) and contained fifteen known protein coding genes. Five of these (GOLPH3; MTMR12; ZFR; SUB1; and NPR3) and an ultra-conserved microRNA (hsa-miR-579) were present in an 883?kb candidate gene region in 5p13.3 that was deleted in the present family but not in previously reported overlapping benign deletions. Members of the cadherin precursor gene cluster, with brain specific expression, were deleted in both affected and benign deletion families. The candidate genes in 5p13.3 may be sufficient to account for the consistent presence or absence of phenotype in medial 5p deletions. However, we consider the possibility of position effects in which CDH6, and/or other cadherin genes, become penetrant when adjacent genes, or modifiers of gene expression, are also deleted. This could account for the absence of intellectual disability in benign deletions of the cadherin cluster, the cognitive phenotype in medial 5p deletion syndrome and the greater severity of intellectual disability in patients with cri-du-chat syndrome and deletions of 5p15 that extend into the region deleted in the present family
A new approach for the identification of common point mutations within the dystrophin gene using MLPA
No full textBetween 70-75% of patients with Duchenne muscular dystrophy (DMD) have a large deletion or duplication of one or more exonsin the dystrophin gene. The remaining patients are likely to have either a micro-deletion, micro-insertion or a point mutation. The Multiplex Ligation-dependent Probe Amplification assay (MLPA) is quick and will detect all whole exonic deletions and duplications [1] however, point mutation analysis of the dystrophin gene remains difficult and time consuming due to the size of the gene. We have designed two MLPA probe mixes which are specific to 23 of the most common dystrophin gene point mutations (17% of all reported dystrophin point mutation cases). These point mutation probe mixes work simultaneously with the two commercial dystrophin MLPA probe mixes (P034/P035 MRC Holland), allowing both full dosage analysis and partial point mutation analysis in a two tube reaction. This method has been validated using nine positive controls
Trust and Trustworthiness in the Fourth and Fifth Estates
No full textThe high contemporary salience in the social sciences of the topics of "trust" and "trustworthiness" has focused attention on the mass media’s putative role in eroding trust. Intrinsically, the absence in the mass media of the dialogic and interactive element to trust building identified by O’ Neill (2002) may suggest that the lack of trust and trustworthiness in the mass media is structural and recent penalties imposed by the UK communication regulator, Ofcom, on UK public service broadcasters including the BBC seem to support such a view. However, drawing on and adapting O’Neill, the author identifies two distinct potential media trust building strategies: one procedural (based in professional norms) and the second dialogic and interactive (nascent in “Web 2.0” applications). Focusing on UK Web 2.0 media sites the author identifies instances where the "dialogic" character of "Web 2.0" has established and enhanced trustworthiness. He argues normatively for a combination of "Web 2.0" interactivity and the adoption and implementation of self-regulatory codes in order to enhance the trustworthiness of the media
The "Illimitable Dominion" of Charles Dickens: Transatlantic Print Culture and the Spring of 1842
No full textThis article explores Edgar Allan Poe’s May 1842 edition of Graham’s Monthly Magazine in the context of debates about international copyright circulating in the press at the time of Charles Dickens’s famous tour of the US. I offer a reading of Poe’s short story ‘The Masque of the Red Death’, and his review of Hawthorne’s Twice-Told Tales that sees these texts as interventions in transatlantic debates at the forefront of the public imagination in the Spring of 1842. In particular, through an original close reading of ‘The Masque of the Red Death’ I demonstrate how Poe subtly drew upon penny press exposés to inform the short story’s discussion of class, status and rights of access. I also suggest that the argument Poe made in his review of Nathaniel Hawthorne about the importance of ‘invention, creation, imagination [and] originality’ to the ‘prose tale’ is usefully considered in the same context, as an American response to questions of authorship that were also raised by the popular hysteria surrounding Dickens
Accuracy of diagnostic testing in primary ciliary dyskinesia
No full textDiagnosis of primary ciliary dyskinesia (PCD) lacks a "gold standard" test and is therefore based on combinations of tests including nasal nitric oxide (nNO), high-speed video microscopy analysis (HSVMA), genotyping and transmission electron microscopy (TEM). There are few published data on the accuracy of this approach.Using prospectively collected data from 654 consecutive patients referred for PCD diagnostics we calculated sensitivity and specificity for individual and combination testing strategies. Not all patients underwent all tests.HSVMA had excellent sensitivity and specificity (100% and 93%, respectively). TEM was 100% specific, but 21% of PCD patients had normal ultrastructure. nNO (30?nL·min(-1) cut-off) had good sensitivity and specificity (91% and 96%, respectively). Simultaneous testing using HSVMA and TEM was 100% sensitive and 92% specific.In conclusion, combination testing was found to be a highly accurate approach for diagnosing PCD. HSVMA alone has excellent accuracy, but requires significant expertise, and repeated sampling or cell culture is often needed. TEM alone is specific but misses 21% of cases. nNO (?30?nL·min(-1)) contributes well to the diagnostic process. In isolation nNO screening at this cut-off would miss ?10% of cases, but in combination with HSVMA could reduce unnecessary further testing. Standardisation of testing between centres is a future priority
Resolving clinical diagnoses for syndromic cleft lip and/or palate phenotypes using whole-exome sequencing
No full textIndividuals from three families ascertained in Bogota, Colombia, showing syndromic phenotypes, including cleft lip and/or palate, were exome sequenced. In each case sequencing revealed underlying causal variation confirming or establishing diagnoses. The findings include very rare and novel variants providing insights into genotype and phenotype relationships. These include the molecular diagnosis of an individual with Nager syndrome and a family exhibiting an atypical Incontinentia Pigmenti phenotype with a missense mutation in IKBKG. IKBKG mutations are typically associated with pre-term male death but this variant is associated with survival for 8–15 days. The third family exhibits unusual phenotypic features and the proband received a provisional diagnosis of Pierre Robin Sequence (PRS). Affected individuals share a novel deleterious mutation in IRF6. Mutations in IRF6 cause Van der Woude and Popliteal pterygium syndrome and contribute to nonsyndromic cleft lip phenotypes but have not previously been associated with a PRS phenotype. Exome sequencing followed by in silico screening to identify candidate causal variant(s), and functional assay in some cases, offers a powerful route to establishing molecular diagnoses. This approach is invaluable for conditions showing phenotypic and/or genetic heterogeneity including cleft lip and/or palate phenotypes where many underlying causal genes have not been identified
Quantification of transmission risk in a male patient with a FLNB mosaic mutation causing Larsen syndrome: implications for genetic counseling in postzygotic mosaicism cases
No full textWe report the case of a male patient with Larsen syndrome found to be mosaic for a novel point mutation in FLNB in whom it was possible to provide evidence-based personalized counseling on transmission risk to future offspring. Using dideoxy sequencing, a low-level FLNB c.698A>G, encoding p.(Tyr233Cys) mutation was detected in buccal mucosa and fibroblast DNA. Mutation quantification was performed by deep next-generation sequencing (NGS) of DNA extracted from three somatic tissues (blood, fibroblasts, saliva) and a sperm sample. The mutation was detectable in all tissues tested, at levels ranging from 7% to 10% (mutation present in ∼20% of diploid somatic cells and 7% of haploid sperm), demonstrating the involvement of both somatic and gonadal lineages in this patient. This report illustrates the clinical utility of performing targeted NGS analysis on sperm from males with a mosaic condition in order to provide personalized transmission risk and offer evidence-based counseling on reproductive safety.</p
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