BackgroundIron overload, diagnosed by means of magnetic resonance imaging (MRI), is an increasingly recognized disorder in hemodialysis patients. Specific MRI protocols have been shown to provide a reliable estimation of tissue iron content in non-renal patient populations but have not been validated in dialysis patients. Such validation studies require liver biopsy for histological comparison, but this invasive and risky procedure raises ethical concerns, especially regarding frail patients with end-stage renal disease.Materials and methodsWe compared in a pilot study Scheuer’s histological classification and Deugnier and Turlin’s histological classification of iron overload (Perls staining) with signal-intensity-ratio MRI values obtained with the Rennes University algorithm in 11 hemodialysis patients in whom liver biopsy was formally indicated for their medical follow-up.ResultsFor Scheuer’s histological classification, the Wilcoxon non-parametric matched-pairs test showed no significant difference in the ranking of iron overload by the two methods eg histology and MRI (sum of ranks = 1.5; p = 1). The MRI and Scheuer’s histological classifications were tightly correlated (rho = 0.866, p = 0.0035, Spearman’s coefficient), as were the absolute liver iron concentrations (LIC) at MRI (rho = 0.860, p = 0.0013, Spearman’s coefficient). The absolute liver iron concentrations at MRI were also highly correlated with Deugnier and Turlin’s histological scoring (rho = 0.841, p = 0.0033, Spearman’s coefficient).ConclusionsThis pilot study shows that liver iron determination based on signal-intensity-ratio MRI (Rennes University algorithm) very accurately identifies iron load in hemodialysis patients, by comparison with liver histology.

Almost all haemodialysis patients are treated with parenteral iron to compensate for blood loss and to allow the full therapeutic effect of erythropoiesis-stimulating agents. Iron overload is an increasingly recognised clinical situation diagnosed by quantitative magnetic resonance imaging (MRI). MRI methods have not been fully validated in dialysis patients. We compared Deugnier's and Turlin's histological scoring of iron overload and Scheuer's classification (with Perls' stain) with three quantitative MRI methods for measuring liver iron concentration (LIC)-signal intensity ratio (SIR), R2* relaxometry, and R2* multi-peak spectral modelling (Iterative Decomposition of water and fat with Echo Asymmetry and Least-squares estimation (IDEAL-IQ ® )) relaxometry-in 16 haemodialysis patients in whom a liver biopsy was formally indicated for medical follow-up. LIC MRI with these three different methods was highly correlated with Deugnier's and Turlin's histological scoring (SIR: r = 0.8329, p = 0.0002; R2* relaxometry: r = −0.9099, p < 0.0001; R2* relaxometry (IDEAL-IQ ® ): r = −0.872, p = 0.0018). Scheuer's classification was also significantly correlated with these three MRI techniques. The positive likelihood ratio for the diagnosis of abnormal LIC by Deugnier's histological scoring was > 62 for the three MRI methods. This study supports the accuracy of quantitative MRI methods for the non-invasive diagnosis and follow-up of iron overload in haemodialysis patients.

A mosaicism is defined by the presence of two or more populations of cells with different genotypes in one individual. Chromosomal germinal mosaicism occurs in germ cells before the onset of meiosis. Previously, few studies have described germinal mosaicism. In this study, we report on two siblings who carried identical pure and direct interstitial 4q22.2q32.3 duplication. Procedure investigations included complete clinical description, conventional cytogenetic analysis, fluorescence in situ hybridization (FISH), comparative genomic hybridization (CGH) array experiments and microsatellite study searching for parental origin of the duplication. Microarray CGH and further FISH experiments with BAC clones showed the same 70.8 Mb direct duplication, dup(4)(q22.2q32.3). Molecular studies of the 4q duplication were consistent with maternal origin associated with mitotic or meiotic rearrangements. This structural chromosomal aberration was associated in both cases with increased nuchal translucency, growth retardation and dysmorphy. Cardiopathy and lung malformations were only evident in the first case. These clinical manifestations are similar to those previously reported in previous studies involving pure 4q trisomy of the same region, except for thumb and renal abnormalities that were not obvious in the presented cases. The amplified region included genes involved in neurological development (NEUROG2, MAB21L2, PCDH10/18 and GRIA2). The recurrent 4q duplication in these siblings is consistent with a maternal ovarian germinal mosaicism. This is the first description of germinal mosaicism for a large chromosomal duplication and highlights that genetic counselling for apparently de novo chromosome aberration should be undertaken with care.

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The occurrence of an additional ring chromosome 20 is a rare chromosome abnormality, and no common phenotype has been yet described. We report on two new patients presenting with a supernumerary ring chromosome 20 both prenatally diagnosed. The first presented with intrauterine growth retardation and some craniofacial dysmorphism, and the second case had a normal phenotype except for obesity. Conventional cytogenetic studies showed for each patient a small supernumerary marker chromosome (SMC). Using fluorescence in situ hybridization, these SMCs corresponded to ring chromosomes 20 including a part of short and long arms of chromosome 20. Detailed molecular cytogenetic characterization showed different breakpoints (20p11.23 and 20q11.23 for Patient 1 and 20p11.21 and 20q11.21 for Patient 2) and sizes of the two ring chromosomes 20 (13.6 Mb for case 1 and 4.8 Mb for case 2). Review of the 13 case reports of an extra r(20) ascertained postnatally (8 cases) and prenatally (5 cases) showed varying degrees of phenotypic abnormalities. We document a detailed molecular cytogenetic chromosomal breakpoints characterization of two cases of supernumerary ring chromosomes 20. These results emphasize the need to characterize precisely chromosomal breakpoints of supernumerary ring chromosomes 20 in order to establish genotype-phenotype correlation. This report may be helpful for prediction of natural history and outcome, particularly in prenatal diagnosis.