Molecular Basis of Congenital Dyserythropoietic Anemia Type I in French Patients.

Blood - Tập 104 - Trang 3709 - 2004
Hannah Tamary1,2, Orly Dgany1, Alexis Proust3, Tanya Krasnov1, Nili Avidan4, Gil Tchernia3, David Geneviève5, Valérie Comier-Darre5, Martine Le Merrer5, Brigitte Bader-Meunier6, Corinne Ferrero-Vacher7, Isaac Yaniv2, Jean Delaunay3
1Pediatric Hematology, Felsenstein Medical Research Center Sackler Faculty of Medicine, Tel Aviv University, Petah Tikva, Israel
2Pediatric Hematology Oncology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel
3Service d'Hématologie, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France
4the Crown Human Genome, The Weizmann Institute of Science, Rehovot, Israel
5CCA de Génétique Departement de Genetique, Hôpital Necker-Enfants Malades, Paris, France
6Service de Pédiatrie Générale, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France
7Hôpital de Cimiez, Nice Cedex 1, France

Tóm tắt

Abstract Congenital dyserythropoietic anemia type I (CDA I) is an inherited disorder characterized by macrocytic anemia and occasionally also by distal bone malformations. The disease has recently been shown to be caused by mutations in the CDAN1 gene, encoding codanin-1. The aim of the study was to characterize the CDAN1 mutations in 12 French patients with CDA I. The clinical data of the 12 French patients (10 kindreds) with CDA I were reviewed. Each of the 28 CDAN1 exons was amplified and sequenced. Half of the patients had a severe disease with prominent neonatal manifestations, complex bone disease, or both. Nine disease-causing mutations were identified: 6 described previously (P1130L, P671L, F869I, R681X, R713W, S1034F) and 3 novel mutations (R687W, F52L and IVS 8 G to A). Seven were missense mutations located in exons 14 to 28. Twenty seven per cent were identified in exon 14. No patient was homozygous for null type mutations. Only in two monozygotic twin patients did we fail to uncover a mutation. Mutations P671L, F52L and R713W were found on four, two and two alleles, respectively. One of the P671L alleles carried a second mutation (R687W). In conclusion the CDAN1 gene is apparently involved in most cases of CDA I in the French patients explored. Our study supports the previous findings that homozygosity for the null type mutations may be lethal, and that CDAN1 mutations are localized mainly in exons 12–28. In the present small group of patients, no apparent phenotype-genotype correlations were observed, in particular concerning abnormalities of the bones. Analysis of a larger number of patients from different ethnic groups is required to further characterize phenotype-genotype correlation in CDA I.

Thông tin
Thông tin xuất bản

Blood

Tập 104

3709

Thông tin tác giả