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Garcon L.,Laboratoire dHematologie | Iolascon A.,Centro Ingegneria Genetica | Iolascon A.,University of Naples Federico II | Pissard S.,Service de Biochimie | And 6 more authors.
Hemoglobin | Year: 2010

A female patient of Portuguese origin, who was born to consanguineous parents, presented with moderate anemia, mild jaundice and splenomegaly. Bone marrow aspiration showed an erythroid hyperplasia and binucleate erythroblasts, evoking a congenital dyserythropoietic anemia, type II (CDA II). Although microcytosis cast some doubt on the diagnosis, investigation was pursued along this line. The CDA II was finally ruled out as underglycosylation of band 3, remnants of endoplasmic reticulum cisternae and mutations in the SEC23B gene were all missing. On the other hand, analysis of the α-globin genes showed a base substitution at codon 125 (CTG→CGG) of the α2-globin gene, ascertaining a homozygosity for Hb Plasencia (HBA2:c.377T>G). This variant has an unstable α chain. In the absence of a thorough work-up, dyserythropoietic anemia associated with hemoglobin (Hb) variants having a moderately unstable α chain, may be mistaken for CDA II. © 2010 Informa Healthcare USA, Inc.

Arnaud L.,National Institute of Blood Transfusion | Saison C.,National Institute of Blood Transfusion | Helias V.,National Institute of Blood Transfusion | Lucien N.,National Institute of Blood Transfusion | And 25 more authors.
American Journal of Human Genetics | Year: 2010

The congenital dyserythropoietic anemias (CDAs) are inherited red blood cell disorders whose hallmarks are ineffective erythropoiesis, hemolysis, and morphological abnormalities of erythroblasts in bone marrow. We have identified a missense mutation in KLF1 of patients with a hitherto unclassified CDA. KLF1 is an erythroid transcription factor, and extensive studies in mouse models have shown that it plays a critical role in the expression of globin genes, but also in the expression of a wide spectrum of genes potentially essential for erythropoiesis. The unique features of this CDA confirm the key role of KLF1 during human erythroid differentiation. Furthermore, we show that the mutation has a dominant-negative effect on KLF1 transcriptional activity and unexpectedly abolishes the expression of the water channel AQP1 and the adhesion molecule CD44. Thus, the study of this disease-causing mutation in KLF1 provides further insights into the roles of this transcription factor during erythropoiesis in humans. © 2010 The American Society of Human Genetics. All rights reserved.

Cali G.,National Research Council Italy | Gentile F.,National Research Council Italy | Mogavero S.,University of Naples Federico II | Pallante P.,National Research Council Italy | And 5 more authors.
Endocrinology | Year: 2012

Cadherin (CDH)16/kidney-specific-cadherin was first described as a kidney-specific adhesion molecule and thereafter found expressed also in the thyroid gland. We show here that CDH16 fully colocalizes with CDH1/E-cadherin on the basolateral plasma membrane of mouse and human thyrocytes. In thyrocyte cultures, the expression of CDH16 is dependent upon TSH, as other thyroid differentiation markers. In the developing mouse thyroid, CDH16 is expressed at embryonic day 10.5, 1-2 d after the main thyroid-specific transcription factors involved in thyroid cell differentiation. In human thyroid carcinomas, as determined by quantitative RT-PCR, CDH16 expression decreases in papillary, follicular, and anaplastic thyroid carcinomas, and the decrease is more pronounced than that of CDH1. Moreover, by immunofluorescence and confocal microscopy, it appears that although CDH16-negative tumor cells may still be positive for CDH1, CDH1-negative cells are also negative for CDH16, indicating a more extensive loss of the latter and suggesting that CDH16 loss might precede that of CDH1. Loss of CDH16 appears to be a marker of epithelialmesenchymal transition as indicated by its decrease in cultured thyroid cells after TGF-β treatment. Finally, the decrease in CDH16 is paralleled in part by the decrease in α B-crystallin, which was proposed to mediate the interaction of CDH16 cytosolic tail with the cell cytoskeleton. In conclusion, CDH16 is a thyroid-selective and hormone-dependent adhesion protein that might play a role during thyroid development and that may be a useful marker to monitor thyroid carcinomas. Copyright © 2012 by The Endocrine Society.

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