Structural rearrangements as a recurrent pathogenic mechanism for SETBP1 haploinsufficiency.

Chromosomal structural rearrangements consist of anomalies in genomic architecture that may or may not be associated with genetic material gain and loss. Evaluating the precise breakpoint is crucial from a diagnostic point of view, highlighting possible gene disruption and addressing to appropriate genotype-phenotype association. Structural rearrangements can either occur randomly within the genome or present with a recurrence, mainly due to peculiar genomic features of the surrounding regions. We report about three non-related individuals, harboring chromosomal structural rearrangements interrupting SETBP1, leading to gene haploinsufficiency. Two out of them resulted negative to Chromosomal Microarray Analysis (CMA), being the rearrangement balanced at a microarray resolution. The third one, presenting with a complex three-chromosome rearrangement, had been previously diagnosed with SETBP1 haploinsufficiency due to a partial gene deletion at one of the chromosomal breakpoints. We thoroughly characterized the rearrangements by means of Optical Genome Mapping (OGM) and Whole Genome Sequencing (WGS), providing details about the involved sequences and the underlying mechanisms. We propose structural variants as a recurrent event in SETBP1 haploinsufficiency, which may be overlooked by laboratory routine genomic analyses (CMA and Whole Exome Sequencing) or only partially determined when associated with genomic losses at breakpoints. We finally introduce a possible role of SETBP1 in a Noonan-like phenotype.

[Optimal use of peritoneal dialysis with multi-disciplinary management]. / Ottimizzazione della terapia dialitica peritoneale attraverso una gestione multidisciplinare.

INTRODUCTION: Considering the increasing incidence of chronic kidney disease and the increased use of peritoneal dialysis, we wanted to assess whether the multidisciplinary management of patients in peritoneal dialysis might produce improvement in the quality of patients' lives when compared to management by a routine team of operators. METHODS: Our study observed 40 patients on peritoneal dialysis in our Department between 2010 and 2012. They were randomly assigned to either group A, the routine team which consisted of a nephrologist and a nurse, or group B, a multidisciplinary team comprising several medical specialists, a nurse, a psychologist and a social worker. Two tests, KDQOL-SF and MMPI-2, were administered to both groups. RESULTS: In group B, the number of days of hospitalization and day hospital were more than 88% lower when compared to group A. The multidisciplinary team achieved better results with the KDQOL-SF test with regards to both emotional and objective dimensions. The Pearson coefficient between the results of the two questionnaires shows how multidisciplinary management can positively influence the perceived well-being of the patient and his or her adherence to treatment. CONCLUSIONS: In a multidisciplinary team, each operator, in addition to his or her specific role, also contributes to the achievement of the overall objective, namely of ensuring an optimal quality of life to the patient on peritoneal dialysis thereby allowing these patients to continue their professional and social lives.

[Glomerulonephritis]. / Le glomerulonefriti.

In glomerulonephritis we find various anatomical and pathological aspects of the kidneys, despite the clinical manifestations are almost identical (haematuria, proteinuria, nephrotic or nephritic syndrome). The anatomical damage and the clinical manifestations is produced by a known or unknown antigenic insult, in relation to the predisposing genetic factors and to the defences predisposed by the immunological system. From the '80, some publications showed an immunological pathogenesis of the glomerulonephritis, with the participation of haematological elements such as lymphoid cells. Therefore, the pathogenesis of the primitive glomerulonephritis are in great part unknown, although we know that the increased permeability of the glomerular capillary is correlated to the production of proinflammatory lymphokines from T cells, which are overexpressed (RANTES). Not to succeed to adequately eliminate these cells can be, thus, a cause of relapse with the final result of renal infiltration and amplification of the immune response.

Gram staining applied to human spermatozoa: a simple method for studying chromatin condensation status.

Gram staining applied to human spermatozoa from fertile donors is described. The stain revealed populations of Gram-positive and Gram-negative spermatozoa. Data showed a significant and progressive decrease in the percentage of Gram-positive spermatozoa at different times during the chromatin decondensation procedure (SDS-BSA and SDS-EDTA). No significant correlation could be found between Gram staining and other functional tests used for spermatozoa; only the aniline blue staining test showed a poor correlation. Our study demonstrates that normal spermatozoa with regular chromatin condensation appear Gram-positive, while spermatozoa with altered chromatin condensation appear Gram-negative.