Two novel missense mutations in FGD4/FRABIN cause Charcot-Marie-Tooth type 4H (CMT4H)

By sequencing of the FGD4 coding sequence in a cohort of 101 patients affected by autosomal recessive demyelinating Charcot-Marie-Tooth disease (CMT), we have identified two novel missense mutations in FGD4 in two patients from consanguineous descent: p.Arg442His in an Algerian patient and p.Met566Ile in a Lebanese girl. The patients present early onset, slowly progressive CMT, with drastic reduction of nerve conduction velocities. These mutations are the second and third missense mutations characterized in FGD4. They are likely to lead to conformational changes in the PH1 and FYVE domains.     

EGFR-Mutated Breast Metastasis of Lung Adenocarcinoma: A Case Report

Breast metastasis from other primary carcinoma is very rare and could be difficult to identify despite immunohistochemistry analysis. Breast metastasis from lung adenocarcinoma can mimic triple-negative breast cancer. Given the prognosis and therapeutic challenges, a correct diagnosis appears essential, and molecular biomarkers could be useful. We report the case of a 52-year-old woman with a breast mass initially diagnosed as primary breast cancer and secondarily attached to breast metastasis from an EGFR-mutated lung adenocarcinoma. The same activating EGFR mutations were identified in both the primary lung carcinoma and the breast metastasis.Key Words: Lung adenocarcinoma, Breast metastasis, EGFR mutation, Triple-negative breast cancer, EGFR tyrosine kinase inhibitors     

Autosomal recessive primary microcephaly due to ASPM mutations: An update

Autosomal recessive microcephaly or microcephaly primary hereditary (MCPH) is a genetically heterogeneous neurodevelopmental disorder characterized by a reduction in brain volume, indirectly measured by an occipitofrontal circumference (OFC) 2 standard deviations or more below the age‐ and sex‐matched mean (?2SD) at birth and ?3SD after 6 months, and leading to intellectual disability of variable severity. The abnormal spindle‐like microcephaly gene (ASPM), the human ortholog of the Drosophila melanogaster “abnormal spindle” gene (asp), encodes ASPM, a protein localized at the centrosome of apical neuroprogenitor cells and involved in spindle pole positioning during neurogenesis. Loss‐of‐function mutations in ASPM cause MCPH5, which affects the majority of all MCPH patients worldwide. Here, we report 47 unpublished patients from 39 families carrying 28 new ASPM mutations, and conduct an exhaustive review of the molecular, clinical, neuroradiological, and neuropsychological features of the 282 families previously reported (with 161 distinct ASPM mutations). Furthermore, we show that ASPM‐related microcephaly is not systematically associated with intellectual deficiency and discuss the association between the structural brain defects (strong reduction in cortical volume and surface area) that modify the cortical map of these patients and their cognitive abilities.     

DNA/Amphiphilic Block Copolymer Nanospheres Promote Low-dose DNA Vaccination

Intramuscular (i.m.) DNA vaccination induces strong cellular immune responses in the mouse, but only at DNA doses that cannot be achieved in humans. Because antigen expression is weak after naked DNA injection, we screened five nonionic block copolymers of poly(ethyleneoxide)-poly(propyleneoxide) (PEO-PPO) for their ability to enhance DNA vaccination using a β-galactosidase (βGal) encoding plasmid, pCMV-βGal, as immunogen. At a high DNA dose, formulation with the tetrafunctional block copolymers 304 (molecular weight [MW] 1,650) and 704 (MW 5,500) and the triblock copolymer Lutrol (MW 8,600) increased βGal-specific interferon-γ enzyme-linked immunosorbent spot (ELISPOT) responses 2–2.5-fold. More importantly, 704 allowed significant reductions in the dose of antigen-encoding plasmid. A single injection of 2 µg pCMV-βGal with 704 gave humoral and ELISPOT responses equivalent to those obtained with 100 µg naked DNA and conferred protection in tumor vaccination models. However, 704 had no adjuvant properties for βGal protein, and immune responses were only elicited by low doses of pCMV-βGal formulated with 704 if noncoding carrier DNA was added to maintain total DNA dose at 20 µg. Overall, these results show that formulation with 704 and carrier DNA can reduce the dose of antigen-encoding plasmid by at least 50-fold.     

Comparison between web-based and paper versions of a self-administered anthropometric questionnaire

Online data collection could advantageously replace paper-and-pencil questionnaires in epidemiological studies by reducing the logistic burden, the cost and the duration of data processing. However, there is a need for studies comparing these new instruments to traditional ones. Our objective was to compare the web-based version of the NutriNet-Santé self-administered anthropometric questionnaire to the paper-based version. The questionnaire included 17 questions divided into subquestions (55 variables in all) dealing with height, weight, hip and waist circumferences, weight history, restrictive diet and weight self-perception. Both versions of the questionnaire were filled out by 147 volunteers (paper version first, N = 76, or web-based version first, N = 71) participating in the SU.VI.MAX (“Supplémentation en VItamines Minéraux et AntioXydants”) cohort (age-range: 49–75 years; men: 46.3%). At the end of the test, subjects filled in a “satisfaction” questionnaire giving their opinions and feelings about each version. Agreement was assessed by intraclass correlation coefficients (ICCs) and kappas. We also quantified the number of errors inherent in the paper version. Agreement between the two versions was high. ICCs ranged from 0.86 to 1.00. Kappas ranged from 0.69 to 1.00 for comparable variables. A total of 82 data entry mistakes (1.5% of total entries), 60 missing values (1.1%), 57 inconsistent values (1.1%) and 3 abnormal values (0.1%) were counted in the paper version (non-existent in the web-based version due to integrated controls). The web-based version was preferred by 92.2% of users. In conclusion, the quality of information provided by the web-based anthropometric questionnaire used in the NutriNet-Santé Study was equal to, or better than, that of the paper version, with substantial logistic and cost advantages.     

Intradermal tacrolimus prevent scar hypertrophy in a rabbit ear model: a clinical,histological and spectroscopical analysis

Background: Keloids and hypertrophic scars (HSc) affect 4.5–16% of the population. Thus far, the different approaches of keloid treatment are not very efficient, with a 50% relapse rate and many ongoing researches are looking for simple, safe and more efficient therapeutic methods. Tacrolimus is an immunomodulator that could be useful in treating keloid. Objectives: The objective of this study is to evaluate the effectiveness of Tacrolimus in inhibiting HSc formation on rabbits' ears model and to check optical skin spectroscopy in tissue characterization. Methods: Our study was carried out on 20 New‐Zealand female white rabbits. HSc were obtained by wounding rabbits' ear. These wounds were treated with intradermal injections of tacrolimus (0.2–0.5 mg/cm²) or a vehicule. The assessment of treatment efficacy was performed by clinical examinations, histological assay and skin spectrometry. Results: Tacrolimus did not induce general or local side‐effects. The scar elevation index in treated subjects was half less than that of the untreated ones. Furthermore, dermal thickness and inflammatory cellular density were both significantly smaller for treated scars than for the control ones. In vivo optical skin spectroscopy can characterize hypertrophic and normal skin with high sensibility and specificity. Conclusion: Intradermal injection of tacrolimus at 0.5 mg/cm² is an efficient way to prevent HSc in our experiment model and its tolerance is correct. Optical spectroscopy could be a good non‐invasive tool to evaluate HSc treatment. These promising results might be proposed for patients suffering from keloid.