Germline mutation p.N363K in POLE is associated with an increased risk of colorectal cancer and giant cell glioblastoma.

Germline mutations of the POLE gene are responsible for polymerase proofreading-associated polyposis syndrome (PPAP). These mutations were hypothesised to predispose to extra-gastrointestinal tumours (ovary, endometrium, brain), but this association has not been confirmed so far. We report a family with an autosomal dominant inheritance of PPAP due to a c.1089C>A; p.Asn363Lys mutation in the proofreading exonuclease domain of POLE. Ten patients presenting a history of colorectal tumours and three patients with polyposis are indexed in this family. Three carriers (including siblings and a distant cousin at 30, 45 and 52 respectively) and another member (at 37 not tested) presented glioblastoma. This is the second family reported to carry this mutation. Among the four glioblastomas in the family that we report, both show similar pathology: giant cell glioblastoma. These cases suggest that the c.1089C>A germline POLE mutation may confer an increased risk of brain cancer [incidence 17.4% (4/23) in mutation carriers combining the two families]. More observations are needed to support this hypothesis. It seems that not all mutations of POLE are equally associated with extra-gastrointestinal tumours. Although carriers of a mutation responsible for PPAP should benefit from screening for colorectal and uterine cancer, due to the rapid evolution of glioblastoma the value of neurological follow-up and brain imaging screening remains questionable. Nevertheless, considering the limitations of standard therapy for glioblastoma, mutation status could be useful for targeting therapy. The biological mechanism linking POLE mutation to glioblastoma remains to be determined.

4q25 microdeletion encompassing PITX2: A patient presenting with tetralogy of Fallot and dental anomalies without ocular features.

Axenfeld-Rieger syndrome (ARS) is a heterogeneous clinical entity transmitted in an autosomal dominant manner. The main feature, Axenfeld-Rieger Anomaly (ARA), is a malformation of the anterior segment of the eye that can lead to glaucoma and impair vision. Extra-ocular defects have also been reported. Point mutations of FOXC1 and PITX2 are responsible for about 40% of the ARS cases. We describe the phenotype of a patient carrying a deletion encompassing the 4q25 locus containing PITX2 gene. This child presented with a congenital heart defect (Tetralogy of Fallot, TOF) and no signs of ARA. He is the first patient described with TOF and a complete deletion of PITX2 (arr[GRCh37]4q25(110843057-112077858)x1, involving PITX2, EGF, ELOVL6 and ENPEP) inherited from his ARS affected mother. In addition, to our knowledge, he is the first patient reported with no ocular phenotype associated with haploinsufficiency of PITX2. We compare the phenotype and genotype of this patient to those of five other patients carrying 4q25 deletions. Two of these patients were enrolled in the university hospital in Toulouse, while the other three were already documented in DECIPHER. This comparative study suggests both an incomplete penetrance of the ocular malformation pattern in patients carrying PITX2 deletions and a putative association between TOF and PITX2 haploinsufficiency.

Automated versus manual sample inoculations in routine clinical microbiology: a performance evaluation of the fully automated InoqulA instrument.

The process of plate streaking has been automated to improve the culture readings, isolation quality, and workflow of microbiology laboratories. However, instruments have not been well evaluated under routine conditions. We aimed to evaluate the performance of the fully automated InoqulA instrument (BD Kiestra B.V., The Netherlands) in the automated seeding of liquid specimens and samples collected using swabs with transport medium. We compared manual and automated methods according to the (i) within-run reproducibility using Escherichia coli-calibrated suspensions, (ii) intersample contamination using a series of alternating sterile broths and broths with >10(5) CFU/ml of either E. coli or Proteus mirabilis, (iii) isolation quality with standardized mixed bacterial suspensions of diverse complexity and a 4-category standardized scale (very poor, poor, fair to good, or excellent), and (iv) agreement of the results obtained from 244 clinical specimens. By involving 15 technicians in the latter part of the comparative study, we estimated the variability in the culture quality at the level of the laboratory team. The instrument produced satisfactory reproducibility with no sample cross-contamination, and it performed better than the manual method, with more colony types recovered and isolated (up to 11% and 17%, respectively). Finally, we showed that the instrument did not shorten the seeding time over short periods of work compared to that for the manual method. Altogether, the instrument improved the quality and standardization of the isolation, thereby contributing to a better overall workflow, shortened the time to results, and provided more accurate results for polymicrobial specimens.

[Gut translocation septicemia in infant]. / Septicémie par translocation d'origine digestive chez l'enfant.

Intestinal microbiotype necessary for life is a source of complications in childhood. Bacterial translocation is responsible of endogenous septicaemia and invasive complications. We report five cases of severe invasive infections associated with diarrhoea, digestive bleeding or sepsis. Biological parameters for inflammation are highly positive, and blood cultures reveal bacterial identification: salmonella enteridis, enterobacter cloacae, campylobacter jejuni, escherichia coli or clostridium difficile. We describe the predisposing factors and susceptibility status to develop translocation: invasive diarrhoea, asplenia, gasto-intestinal disease… All invasive infections in children require etiological approach with the possibility of an endogenous septicaemia (bacterial translocation). This approach minimises the nosocomial features undercurrent in these invasive infections, and leads also to other alternative preventive measures: antibiotic association, maintaining an enteral nutrition, pre or probiotic use, specific digestive decontamination.

[Epidemiology of Human Metapneumovirus in respiratory tract diseases of children: preliminary results]. / Epidémiologie du métapneumovirus humain dans les infections respiratoires de l'enfant: résultats préliminaires.

BACKGROUND: Human metapneumovirus (hmpv) is a newly identified agent responsible for respiratory tract infections in children, especially before one year of age. A prospective epidemiological study is underway to better define the spectrum of the disease in France. PATIENTS AND METHODS: From November 2003 to November 2004, rhinopharyngeal aspirates were obtained from all children under five years of age admitted to the hospital with upper or lower airway symptoms. Viral identification was made using gene amplification. RESULTS: Among 355 evaluable samples to date, 34 were positive for hmpv genome. Mean age of infected children was 6.4 months, 20.5% were prematurely born infants. The prognosis is usually good. CONCLUSION: Our preliminary results are consistent with the available literature data. Further studies are needed to better define the exact frequency and morbidity of this newly recognized infection, both in hospital and community settings.