Recurrent microdeletion at 17q12 as a cause of Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome: two case reports

<p>Abstract</p> <p>Background</p> <p>Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH) consists of congenital aplasia of the uterus and the upper part of vagina due to anomalous development of Müllerian ducts, either isolated or associated with other congenital malformations, including renal, skeletal, hearing and heart defects. This disorder has an incidence of approximately 1 in 4500 newborn girls and the aetiology is poorly understood.</p> <p>Methods and Results</p> <p>we report on two patients affected by MRKH syndrome in which array-CGH analysis disclosed an identical deletion spanning 1.5 Mb of genomic DNA at chromosome 17q12. One patient was affected by complete absence of uterus and vagina, with bilaterally normal ovaries, while the other displayed agenesis of the upper part of vagina, right unicornuate uterus, non cavitating rudimentary left horn and bilaterally multicystic kidneys. The deletion encompassed two candidate genes, <it>TCF2 </it>and <it>LHX1</it>. Mutational screening of these genes in a selected group of 20 MRKH females without 17q12 deletion was negative.</p> <p>Conclusion</p> <p>Deletion 17q12 is a rare albeit recurrent anomaly mediated by segmental duplications, previously reported in subjects with developmental kidney abnormalities and diabetes. The present two patients expand the clinical spectrum associated with this imbalance and suggest that this region is a candidate locus for a subset of MRKH syndrome individuals, with or without renal defects.</p

ANCA-associated vasculitis in childhood: Recent advances

Abstract Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides are rare systemic diseases that usually occur in adulthood. They comprise granulomatosis with polyangiitis (GPA, Wegener’s), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome). Their clinical presentation is often heterogeneous, with frequent involvement of the respiratory tract, the kidney, the skin and the joints. ANCA-associated vasculitis is rare in childhood but North-American and European cohort studies performed during the last decade have clarified their phenotype, patterns of renal involvement and their prognostic implications, and outcome. Herein, we review the main clinical and therapeutic aspects of childhood-onset ANCA-associated vasculitis, and provide preliminary data on demographic characteristics and organ manifestations of an Italian multicentre cohort

Glomerular autoimmune multicomponents of human lupus nephritis in vivo: α-enolase and annexin AI

Renal targets of autoimmunity in human lupus nephritis (LN) are unknown. We sought to identify autoantibodies and glomerular target antigens in renal biopsy samples from patients with LN and determine whether the same autoantibodies can be detected in circulation. Glomeruli were microdissected from biopsy samples of 20 patients with LN and characterized by proteomic techniques. Serum samples from large cohorts of patients with systemic lupus erythematosus (SLE) with and without LN and other glomerulonephritides were tested. Glomerular IgGs recognized 11 podocyte antigens, with reactivity varying by LN pathology. Notably, IgG2 autoantibodies against α-enolase and annexin AI were detected in 11 and 10 of the biopsy samples, respectively, and predominated over other autoantibodies. Immunohistochemistry revealed colocalization of α-enolase or annexin AI with IgG2 in glomeruli. High levels of serum anti-α-enolase (>15 mg/L) IgG2 and/or anti-annexin AI (>2.7 mg/L) IgG2 were detected in most patients with LN but not patients with other glomerulonephritides, and they identified two cohorts: patients with high anti-α-enolase/low anti-annexin AI IgG2 and patients with low anti-α-enolase/high anti-annexin AI IgG2. Serum levels of both autoantibodies decreased significantly after 12 months of therapy for LN. Anti-α-enolase IgG2 recognized specific epitopes of α-enolase and did not cross-react with dsDNA. Furthermore, nephritogenic monoclonal IgG2 (clone H147) derived from lupus-prone MRL-lpr/lpr mice recognized human α-enolase, suggesting homology between animal models and human LN. These data show a multiantibody composition in LN, where IgG2 autoantibodies against α-enolase and annexin AI predominate in the glomerulus and can be detected in serum

Effects of a multidisciplinary care program on disability, autonomy, and nursing needs in subjects recovering from acute respiratory failure in a chronic ventilator facility

BACKGROUND: The aim of this study was to analyze the effects of a multidisciplinary program carried out in a chronic ventilator facility on disability, autonomy, and nursing needs of patients after a prolonged ICU stay. Secondary outcome measures were survival, weaning rate, chronic ventilator facility stay, and discharge destination. METHODS: Multidisciplinary assessment, clinical stabilization, weaning attempts, and a new Disabled Patients Autonomy Planning tool to assess daily care needs were investigated in 240 subjects in a chronic ventilator facility (52 subjects after cardiovascular surgery, 60 subjects with acute respiratory failure, 71 subjects with COPD, and 57 subjects with neurological disease). RESULTS: At admission, nursing needs, disability, and autonomy differed according to diagnosis (P<.001); weaned subjects had greater nursing needs (P<.001) and disability (P =.0014) than unweaned subjects. During the stay, 13.8% of the subjects died irrespective of diagnosis (P =.12);47%(P <.001) were weaned with significant differences (P <.007) by diagnosis. In the 207 surviving subjects, nursing needs increased as disability increased (r = 0.59, P <.001) and autonomy decreased (r = –0.66, P <.001); disability and autonomy were interrelated (r = 0.61, P <.001). Oxygen saturation, hypercapnia, dyspnea, disability, autonomy, and nursing needs significantly improved (all, P <.001). Fifty-nine percent of the subjects were discharged home. Subjects discharged to nursing homes presented mainly neurological diseases, being more disabled and less autonomous, with higher nursing needs (all, P <.04). Mechanical ventilation use and tracheostomy increased the probability of being discharged to a nursing home (odds ratio [OR] of 1.84, P =.04; OR 2.47, P =.003, respectively). Mortality was higher in subjects who were ventilated (OR 8.44, P <.001), male (OR 2.64, P =.01), elderly (P <.001), or malnourished (P =.01) and in subjects with low autonomy (P <.001), greater nursing needs (P =.002), and more severe disabilities (P =.04). CONCLUSIONS: A specialized tailored multidisciplinary program in subjects after an ICU stay contributed to recovery from disability, autonomy, and fewer nursing needs irrespective of diagnosis. Subjects discharged to a nursing home were the most severely disabled

Making Plans and Spot Decisions

Enlace a video en sitio webBy the end of this lesson the student will be able to talk about his/her plans using present continuous and “be going to”.As well as he/she will be able to describe in simple terms aspects of his/her background, immediate environment and matters in areas of immediate need.STUDIU

Quantities

Enlace a video en sitio webBy the end of this lesson the student will be able to use different measures to ask certain amount of portions and also identify the similarities between quantites.STUDIU

Where are you from?

Enlace a video en sitio webBy the end of this lesson the student will be able to name some countries and nationalities and practice some ways to ask about people’s nationalities. As well as he/she will be able to introduce him/herself.STUDIU

Alport syndrome: impact of digenic inheritance in patients management.

none16noAlport syndrome (ATS) is a genetically heterogeneous nephropathy with considerable phenotypic variability and different transmission patterns, including monogenic (X-linked/autosomal) and digenic inheritance. Here we present a new series of families with digenic inheritance and we discuss consequences for genetic counseling and risk assessment. Out of 5 families harboring variants in more than one COL4 gene detected by Next Generation Sequencing (NGS), minigene splicing assay allowed us to identify four as true digenic. Two families showed COL4A3/A4 mutations in cis, mimicking an autosomal dominant inheritance with a more severe phenotype and one showed COL4A3/A4 mutations in trans, mimicking an autosomal recessive inheritance with a less severe phenotype. In a fourth family a de novo mutation (COL4A5) combined with an inherited mutation (COL4A3) triggered a more severe phenotype. A fifth family, predicted digenic on the basis of silico tools, rather showed monogenic X-linked inheritance due to a hypomorphic mutation, in accordance with a milder phenotype. In conclusion, this study highlights the impact of digenic inheritance in ATS and explains the associated atypical presentations. More complex inheritance should be therefore considered when reviewing prognosis and recurrence risks. On the other side, these findings emphasize the importance to accompany NGS with splicing assays in order to avoid erroneous identification of at risk members.restrictedFallerini, C; Baldassarri, M; Trevisson, E; Morbidoni, V; La Manna, A; Lazzarin, R; Pasini, A; Barbano, G; Pinciaroli, Ar; Garosi, G; Frullanti, E; Pinto, Am; Mencarelli, Ma; Mari, F; Renieri, A; Ariani, F .Fallerini, C; Baldassarri, M; Trevisson, Eva; Morbidoni, Valeria; La Manna, A; Lazzarin, R; Pasini, A; Barbano, G; Pinciaroli, Ar; Garosi, G; Frullanti, E; Pinto, Am; Mencarelli, Ma; Mari, F; Renieri, A; Ariani, F.

Clinical Features and Long-Term Outcome of Nephrotic Syndrome Associated with Heterozygous NPHS1 and NPHS2 Mutations

Background and objectives: Mutations in nephrin (NPHS1) and podocin (NPHS2) genes represent a major cause of idiopathic nephrotic syndrome (NS) in children. It is not yet clear whether the presence of a single mutation acts as a modifier of the clinical course of NS