Recurrence and Familial Inheritance of Intronic NIPBL Pathogenic Variant Associated With Mild CdLS

Splicing pathogenic variants account for a notable fraction of NIPBL alterations underlying Cornelia de Lange syndrome but are likely underrepresented, due to overlooking of non-canonical intronic variants by traditional and contemporary sequencing methods. We describe five subjects, belonging to three families, displaying a mild Cornelia de Lange syndrome phenotype who carry the NIPBL pathogenic variant c.5329–15A>G, affecting the IVS27 branch site, yet reported in a single case. By RNA analysis we evidenced two alternative transcripts: the exon 28 in frame skipped transcript, described in the published case and an out-of-frame transcript retaining 14 nucleotides of IVS27 3′end. Even if both aberrant transcripts are at negligible levels, their presence justifies the CdLS phenotype shared by our patients consisting of borderline-mild cognitive impairment and slight but typical facial dysmorphisms. Transmission of the pathogenic variant from pauci-symptomatic mother to her siblings emphasizes the need of molecular diagnosis extended to deep intronic regions in patients with subtle but recognizable CdLS phenotype

Functional and pharmacological evaluation of novel GLA variants in Fabry disease identifies six (two de novo) causative mutations and two amenable variants to the chaperone DGJ

Abstract Background Allelic heterogeneity is an important feature of the GLA gene for which almost 900 known genetic variants have been discovered so far. Pathogenetic GLA variants cause alpha-galactosidase A (α-Gal A) enzyme deficiency leading to the X-linked lysosomal storage disorder Fabry disease (FD). Benign GLA intronic and exonic variants ( e.g. pseudodeficient p.Asp313Tyr) have also been described. Some GLA missense variants, previously deemed to be pathogenetic ( e.g. p.Glu66Gln and p.Arg118Cys), they have been reclassified as benign after re-evaluation by functional and population studies. Hence, the functional role of novel GLA variants should be investigated to assess their clinical relevance. Results We identified six GLA variants in 4 males and 2 females who exhibited symptoms of FD: c.159C>G p.(Asn53Lys), c.400T>C p.(Tyr134His), c.680G>C (p.Arg227Pro), c.815A>T p.(Asn272Ile), c.907A>T p.(Ile303Phe) and c.1163_1165delTCC (p.Leu388del). We evaluated their impact on the α-Gal A protein by bioinformatic analysis and homology modelling, by analysis of the GLA mRNA, and by site-directed mutagenesis and in vitro expression studies. We also measured their responsiveness to the pharmacological chaperone DGJ. Conclusions The six detected GLA variants cause deficient α-Gal A activity and impairment or loss of the protein wild-type structure. We found p.Asn53Lys and p.Ile303Phe variants to be susceptible to DGJ

Modulation of Light and Nitrogen for Quality-Traits Improvement: A Case Study of Altino Sweet Pepper

Local varieties are known to cope more efficiently with stressful and/or low-input conditions than cultivated ones by activating secondary metabolisms and, hence, are supposed to have higher nutraceutical potential. In this work, we investigate the effects of N and light, supplied at optimal and sub-optimal levels, on the fruit yield and quality of a local ecotype of sweet pepper, Altino, grown in the Abruzzo Region (Southern Italy). In 2017, two open-field experiments were carried out, comparing increasing N rates (0, 100 and 200 kg N ha−1, 0_N, 100_N and 200_N, respectively) and different percentages of shading and/or manipulations of the transmitted solar radiation, obtained through photoselective nets (red net, RN; black net, BN; unshaded Control). Both N and light were preconditions to obtain stable yields in terms of both fruit number and fruit weights. However, BN significantly reduced the number of sunscalded fruits (0.39 vs. 3.38 and 2.59 fruit plant−1 for BN, Control and RN, respectively), leading to lower waste. N deficiency favoured higher total polyphenol (TPC) and flavonoid (TFC) contents in ripened fruits; on the other hand, shading significantly reduced TPC (−12.4%) in immature and TFC (−18.2%) in red fruits. The variations in nutraceuticals were also evaluated in terms of the variations of the single phenolic acids in fruits during ripening; the most interesting results were associated with light treatments. Further research should be directed to the in-depth study of nutrition regimes, in combination with other photoselective nets applications (i.e., pearl nets), that could be suitable for the Altino genotype to enhance the yield and nutraceutical potentials of its fruits

Optimal Position of A Long-Term Central Venous Catheter Tip in A Pediatric Patient with Congenital Diseases

Progress in medical and scientific research has increased the chances of survival for young patients with congenital diseases, children who, in the past, would not have had any chance of survival. Nowadays, congenital diseases can be treated with appropriate replacement therapies. These treatments can be difficult to administer in young patients because of the high frequency of administration (sometimes more than a dose per week), the use of intravenous infusion and the long-term or life-term requirement

Oligosaccharides in 4 different milk groups, Bifidobacteria, and Ruminococcus obeum.

Objectives: The aim was of this study is to identify a link between the total amount of breast milk oligosaccharides and faecal microbiota composition of newborns at the end of the first month of life, with special attention paid to bifidobacteria, and establish the role, if any, of the different oligosaccharides in determining the gut microbiota composition. Subjects and Methods: Milk oligosaccharide groups were identified by high-performance anion exchange chromatography analysis. DPCRNA from newborns\u2019 faecal samples at 30 days of life was isolated and processed by polymerase chain reaction analyses that allow the identification of 6 species of bifidobacteria (adolescentis, bifidum, breve, catenulatum, longum, infantis) and Ruminococcus spp; denaturing gradient gel electrophoresis analysis was also performed. Results: No substantial differences in bifidobacteria species composition within milk groups 1, 2, and 3 were observed; however, infants fed with group 4 milk show a microbiota characterised by a greater frequency of Bifidobacteria adolescentis and the absence of Bifidobacteria catenulatum. For the first time, a high percentage of the Ruminococcus genus in infants fed with all milk groups was found. Conclusions: Our data show that milk groups 1, 2, and 3, containing an amount of oligosaccharides ranging within 10 to 15 g/L, share a substantially identical composition of the intestinal microbiota in breast-fed infants, despite quali-quantitative difference in oligosaccharides content. Newborns taking milk with only 5 g/L of oligosaccharides (group 4) harbour a different intestinal microbiota

Italian multicentre study found infectious and vaccine-preventable diseases in children adopted from Africa and recommends prompt medical screening

Aim: This study evaluated the prevalence of infectious diseases and immunisation status of children adopted from Africa. Methods: We studied 762 African children referred to 11 Italian paediatric centres in 2009\u20132015. Clinical and laboratory data were retrospectively collected and analysed. Results: The median age of the children (60.3% males) was 3 years and 6 months, 52.6% came from Ethiopia and 50.1% had at least one infectious disease. Parasitic infections accounted for the majority of the infectious diseases (409 of 715), and the most common were Giardia lamblia (n = 239), Toxocara canis (n = 65) and skin infections (n = 205), notably Tinea capitis/corporis (n = 134) and Molluscum contagiosum (n = 56) Active tuberculosis (TB) was diagnosed in nine children (1.2%). Latent TB infections were diagnosed in 52 (6.8%) children, and only 23 had concordant positive tuberculin skin tests and Quantiferon Gold In-Tube results. Discordant results were associated with Bacille de Calmette-Gu\ue9rin vaccinations (odd ratio 6.30 and 95% confidence interval of 1.01\u201339.20, p = 0.011). Nonprotective antitetanus or antihepatitis B antibody titres were documented in 266 (34.9%) and 396 (51.9%) of the 762 children. Conclusion: The prevalence of infectious conditions and not-protective titres for vaccine-preventable diseases observed in our population underlines the need for prompt and complete medical screening of children adopted from Africa

p.Arg1809Cys substitution in neurofibromin is associated with a distinctive NF1 phenotype without neurofibromas

Analysis of 786 NF1 mutation-positive subjects with clinical diagnosis of neurofibromatosis type 1 (NF1) allowed to identify the heterozygous c.5425C>T missense variant (p.Arg1809Cys) in six (0.7%) unrelated probands (three familial and three sporadic cases), all exhibiting a mild form of disease. Detailed clinical characterization of these subjects and other eight affected relatives showed that all individuals had multiple cafè-au-lait spots, frequently associated with skinfold freckling, but absence of discrete cutaneous or plexiform neurofibromas, Lisch nodules, typical NF1 osseous lesions or symptomatic optic gliomas. Facial features in half of the individuals were suggestive of Noonan syndrome. Our finding and revision of the literature consistently indicate that the c.5425C>T change is associated with a distinctive, mild form of NF1, providing new data with direct impact on genetic counseling and patient management