Signal-intensity-ratio MRI accurately estimates hepatic iron load in hemodialysis patients

Background: Iron 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 methods: We 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. Results: For 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). Conclusions: This 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

Recurrent 70.8 Mb 4q22.2q32.3 duplication due to ovarian germinal mosaicism

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