Familial adenomatous polyposis (FAP), an autosomal dominantly inherited condition accounting for about 1% of all colorectal cancers, results from mutations in the adenomatous polyposis coli (APC) tumor suppressor gene. The clinical spectrum and severity of FAP varies greatly with the mutation site, and both between and within families. Using the protein truncation test, single strand conformation polymorphism analysis and DNA sequencing, we identified 30 (75%) mutant alleles in 40 unrelated FAP families, for a total of 22 different APC mutations. Of these, 18 are known and 4 are novel: c.1797C>A (C599X), c.893_894delAC, (c.3225T>A; c.3226C>A) and c.4526_4527insT. Of the 30 APC gene mutations, 5 (approximately 17%) are nonsense mutations, 17 (approximately 57%) are small deletions, 5 (approximately 17%) are small insertions and 3 (approximately 10%) are complete deletions. All mutations occurred in single pedigrees, except those at codons 1061 and 1062, each found in two unrelated families, and the mutation at codon 1309 in exon 15, found in five unrelated families. About 40% of mutations, mostly small deletions and insertions, are located at repeated sequences; they promote misalignment-mediated errors in DNA replication and could represent a hot spot mutation region. This study enlarges the spectrum of APC gene mutations and sheds light on the correlation between the site of APC germline mutations and clinical manifestations of FAP.

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We examined the adenomatous polyposis coli (APC) gene for disease-causing mutations in 51 unrelated Argentinean probands affected by familial adenomatous polyposis (FAP).Using a combination of the protein truncation test, the single strand conformation polymorphism technique, DNA sequencing and quantitative PCR analysis, we identified the specific mutation in 39 (average age: 28.4 years) of the 51 probands (detection rate: 76.47%); 13 are novel germline mutations and one is a novel sequence variant. There were 27 small deletions, four small duplications, five nonsense mutations in exon 15, three nonsense mutations in exons 6, 11, and 12, and one sequence variant in exon 3 identified in a patient bearing a truncating mutation in exon 15. The most common mutation (found in 10 cases) was at codon 1309. All patients negative for APC mutations were also negative for the MutY homolog (MYH) gene mutation, as expected because of fully penetrant FAP cases. This study enlarges the spectrum of APC gene mutations, and reinforces the concept of mutation heterogeneity. It also sheds light on correlations between the site of APC germline mutations and the clinical manifestations of FAP. Our data indicate that the genotype/phenotype correlations in Argentinean patients are similar to those observed in other populations.

A point-of-care ultrasound scan (POCUS) is a core element of the Royal College of Emergency Medicine (RCEM) specialty training curriculum. However, POCUS documentation quality can be poor, especially in the time-pressured environment of the emergency department (ED). A survey of 10 junior ED clinicians at the Princess Royal University Hospital (PRUH) found that total POCUS documentation was as low as 38% in some examinations.This quality improvement project aimed to increase the coverage and quality of POCUS documentation in the ED. This was done by using a plan-do-study-act (PDSA) regime to improve the quality of POCUS documentation from the original baseline to 80%. There were three discreet PDSA cycles and the interventions included improving education and training about POCUS documentation and the introduction of an original proforma, which incorporated six minimum requirements for POCUS documentation as per the joint RCEM and Royal College of Radiologists (RCR) guidelines for POCUS documentation (patient details, indications, findings, conclusions, signature and date).The project team audited the quality of all documented scans in the resuscitation department of the PRUH against the RCEM/RCR guidelines at baseline and following three discrete PDSA cycles. This was done over an 8-week period, spanning 696 attendances to the resuscitation area of the ED and 42 documented POCUS examinations.Quality recording of the six RCEM/RCR elements of POCUS documentation was poor at baseline but improved following three successful PDSA cycles. There was a demonstrated improvement in five of six documentation elements: patient details on POCUS documentation increased from 53.3% to the 66.7%, indication from 60.0% to 66.7%, conclusion from 13.0% to 83.0%, signature from 86.7% to 100.0% and date from 46.7% to 66.7%.These results suggest that the introduction of a proforma and a vigorous education strategy are effective ways to improve the quality of documentation of ED POCUS.

The etiology of Gerhardt's syndrome is uncertain. With the present work the authors present a hereditary form of this syndrome, which was found in three subsequent generations with autosomal dominant transmission.