Syndrome hémolytique et urémique atypique familial lié à une nouvelle mutation du CFHR 1

POITIERS-BU Médecine pharmacie (861942103) / SudocSudocFranceF

HOX genes are expressed in bovine and mouse oocytes and early embryos.

HOX proteins are transcription factors that play a major role in patterning the body axis of vertebrates from the gastrulation stage. While nothing has been reported so far about their roles at earlier stages, there is evidence that some HOX genes are expressed before gastrulation. The objective of this work was to study the pattern of expression of several HOX genes during oocyte maturation and early embryonic development up to the blastocyst stage. Using nested PCR, HOXD1, HOXA3, HOXD4, HOXB7, HOXB9, and HOXC9 transcripts were detected in bovine oocytes and early embryos at various frequencies depending on the stage of development. Quantitative PCR was performed on bovine oocytes and early embryos: relative expression of HOXD1, HOXA3, and HOXC9 decreased sharply after the 5-8 cell stage. HOXB9 relative expression increased between the oocyte and the morula stage. All transcripts seemed to be of maternal origin before the maternal to embryonic transition, as demonstrated by blocking transcription with α-amanitin. Reverse transcription was performed with either hexamers or oligo-dT, allowing for the determination that HOXC9 transcripts were slightly deadenylated during oocyte maturation; HOXD1, HOXA3, and HOXB9 transcripts were not, indicating that they could be translated. Hoxd1, Hoxa3, Hoxb9, and Hoxc9 expression was also detected in mouse oocytes and early embryos. A similar pattern of expression was found in the two species. In conclusion, mammalian HOX genes might be implicated in the control of oocyte maturation, the maternal-to-embryonic transition or the first steps of embryo differentiation

Zinc Therapy for Wilson Disease in Children in French Pediatric Centers:

International audienceBackground and Aims: Zinc therapy is considered a good option in Wilson disease (WD), as a first-line treatment in presymptomatic children and a maintenance therapy after the initial chelator therapy. The aim of the study was to determine the practical use of zinc treatment in French pediatric centers. Methods: A national survey was conducted in the 6 French centers using zinc acetate to treat WD. Clinical and biological parameters, dosage, and outcome were recorded. Results: A total of 26 children were reported to be treated with zinc acetate, alone or in association with chelators. Of the 9 children (35%) who received zinc alone as a first-line therapy, 2 were switched to D-penicillamine because of inefficacy and 7 remained on zinc alone, but serum transaminase levels normalized in only 4 of them. Five children (19%) were initially treated with zinc in association with D-penicillamine (n = 4) or Trientine (n = 1) with good efficacy. Among the 12 children (46%) who received zinc as a maintenance therapy after D-penicillamine, no relapse of hepatic cytolysis occurred during a median follow-up of 5.2 years, but 2 of them were switched to Trientine because of zinc-related adverse effects. Epigastric pain was observed in 4 children, and a gastric perforation occurred in 1 child. Conclusions: The present study demonstrates poor efficacy of zinc as first-line therapy to control liver disease in half presymptomatic children and a high incidence of related gastrointestinal adverse effects in children with WD

Dynamic Pattern of HOXB9 Protein Localization during Oocyte Maturation and Early Embryonic Development in Mammals.

We previously showed that the homeodomain transcription factor HOXB9 is expressed in mammalian oocytes and early embryos. However, a systematic and exhaustive study of the localization of the HOXB9 protein, and HOX proteins in general, during mammalian early embryonic development has so far never been performed.The distribution of HOXB9 proteins in oocytes and the early embryo was characterized by immunofluorescence from the immature oocyte stage to the peri-gastrulation period in both the mouse and the bovine. HOXB9 was detected at all studied stages with a dynamic expression pattern. Its distribution was well conserved between the two species until the blastocyst stage and was mainly nuclear. From that stage on, trophoblastic cells always showed a strong nuclear staining, while the inner cell mass and the derived cell lines showed important dynamic variations both in staining intensity and in intra-cellular localization. Indeed, HOXB9 appeared to be progressively downregulated in epiblast cells and only reappeared after gastrulation had well progressed. The protein was also detected in the primitive endoderm and its derivatives with a distinctive presence in apical vacuoles of mouse visceral endoderm cells.Together, these results could suggest the existence of unsuspected functions for HOXB9 during early embryonic development in mammals

MYH9-related disorders display heterogeneous kidney involvement and outcome

International audienceBackgroundMYH9-related diseases (MYH9-RD) are autosomal dominant disorders caused by mutations of the MYH9 gene encoding the non-muscle myosin heavy chain IIA. They are characterized by congenital thrombocytopenia, giant platelets and leucocyte inclusions. Hearing impairment, pre-senile cataract and nephropathy can also occur. We aimed to evaluate renal involvement and outcome in MYH9-RD patients followed-up by nephrologists.MethodsWe conducted a retrospective multicentre observational study of 13 patients among 9 families with MYH9 mutation diagnosed by genetic testing and immunofluorescence assay referred to nephrologists.ResultsAt initial referral, median age was 30 (range 14–76) years. Median estimated glomerular filtration rate was 66 mL/min/1.73 m2 (0–141) and two patients had already end-stage renal disease (ESRD). Renal presentation associated proteinuria (n = 12), haematuria (n = 6) and hypertension (n = 6). Three patients developed a rapid onset ESRD whereas five others had a relatively stable kidney function over a 3-year median follow-up (1–34). Extra-renal features varied widely, with hearing impairment in six patients, cataract in two and mild liver dysfunction in seven. Thrombocytopenia existed at referral in 11 patients. Time to diagnosis varied from 0 to 29 years (median 3 years). Initial diagnoses such as idiopathic thrombocytopenic purpura (n = 4) and focal segmental glomerulosclerosis (n = 1) led to corticosteroid administration (n = 4), intravenous immunoglobulins (n = 3), cyclophosphamide (n = 1) and splenectomy (n = 1).ConclusionsRenal involvement and outcome in MYH9-RD are heterogeneous. The diagnosis is often delayed and misdiagnoses can lead to unnecessary treatments. MYH9-RD should be considered in any patient with glomerular involvement associated with a low or slightly decreased platelet count and/or hearing loss and liver dysfunction

Mouse and bovine HOXB9 protein distribution in oocytes and from zygotes to blastocysts.

<p><b>A-C:</b> Whole-mount immunofluorescence of <i>in vitro</i> cultured mouse <b>(A)</b> and <i>in vitro</i> produced bovine <b>(B)</b> embryos. Immature oocyte (IO); mature oocyte (MO); 1-cell embryo (1c); 2-cell embryo (2 c); 5- to 8-cell embryo (5–8 c); 9- to 16-cell embryo (9–16 c); mouse pre-compaction stage (E2.5); bovine compact morula (D5); mouse blastocyst (E3.6) and bovine blastocyst (D7.5). Negative control without primary antibody are shown for E2.5 mouse embryos (E2.5 C-) and bovine IO (IO C-). <b>(C)</b> Zoom on bovine HOXB9 distribution at the metaphasic plate of mature oocyte. Nuclei: Blue; HOXB9: Red. The asterisk depicts polar body. White arrow shows metaphasic plate. Representative confocal Z-section. Scale bar = 20 μm (mouse) or 50 μm (bovine).</p

Mouse HOXB9 protein distribution in <i>in vivo</i> peri-gastrulating embryos: E7.5 and E7.8.

<p><b>A-C:</b> Whole-mount immunofluorescence. <b>(A)</b> E7.5 late allantoic bud stage (LB). <b>(B)</b> E7.5 early headfold—late headfold stage (EHF—LHF). <b>(C)</b> E7.8 first somites stage. Zoom on allantois <b>(C2)</b>. 1. node; 2. notochord; 3. allantois; 4. mesothelium of the allantois; 5. primitive streak; 6. embryonic visceral endoderm. Nuclei: Blue; HOXB9: Red; T: Green. Representative confocal Z-section. Scale bar = 20 μm.</p

In-depth study of mouse and bovine HOXB9 protein distribution during the first step of cell differentiation.

<p><b>A-C:</b> Mouse HOXB9 protein distribution. <b>D-E:</b> Bovine HOXB9 protein distribution. <b>(A-B, D)</b> Whole-mount immunofluorescence. Mouse compact morula at embryonic day E2.8 (E2.8); mouse blastocyst at E3.3 and E3.6 and bovine blastocyst at day 6, 7.5 and 8 post-insemination (D6, D7.5 and D8). Nuclei: Blue; HOXB9: Red; CDX2: Green. Representative confocal Z-section. Scale bar = 20 μm (mouse) or 50 μm (bovine). <b>(C, E)</b> Quantification of relative fluorescence corresponding to nuclear HOXB9 proteins. The boxplot depicts the distribution of the ratios. The ends of the whiskers represent the lowest or the highest datum still within 1.5 x interquartile range. Dots correspond to outliers. N = number of analyzed embryos. * Significant difference (Linear mixed model, * = 0.01 < p < 0.05, **** = p < 0.0001).</p

Mouse and bovine HOXB9 protein distribution during primitive endoderm formation.

<p><b>A-C:</b> Whole-mount immunofluorescence. <b>(A)</b> Mouse <i>in vivo</i> blastocyst at E4.5. a—b: Zoom on epiblast. <b>(B)</b> Bovine <i>in vitro</i> blastocysts at day 7, 8, 8.5 and 9 post-insemination (D7; D8; D8.5 and D9) and <i>in vivo</i> embryos at day 11 post-insemination (D11). Arrows point to GATA6 positive cells that could correspond to primitive endoderm cells. Zoom on D11 bovine embryo <b>(a)</b>. 1. epiblast; 2. primitive endoderm; 3. trophectoderm. <b>(C)</b> Bovine blastocyst produced <i>in vivo</i> at D7. Merge C-: negative control without primary antibody. Nuclei: Blue; HOXB9: Red; GATA4/GATA6: Green; CDX2: Pink. Representative confocal Z-section. Scale bar = 20 μm (mouse) or 50 μm (bovine).</p