title: Congenital dyserythropoietic anemia type I is caused by mutations in codanin-1.
abstract: Congenital dyserythropoietic anemias (CDAs) constitute a rare group of inherited red-blood-cell disorders associated with dysplastic changes in late erythroid precursors. CDA type I (CDAI [MIM 224120], gene symbol CDAN1) is characterized by erythroid pathological features such as internuclear chromatin bridges, spongy heterochromatin, and invagination of the nuclear membrane, carrying cytoplasmic organelles into the nucleus. A cluster of 45 highly inbred Israeli Bedouin with CDAI enabled the mapping of the CDAN1 disease gene to a 2-Mb interval, now refined to 1.2 Mb, containing 15 candidate genes on human chromosome 15q15 (Tamary et al. 1998). After the characterization and exclusion of 13 of these genes, we identified the CDAN1 gene through 12 different mutations in 9 families with CDAI. This 28-exon gene, which is transcribed ubiquitously into 4738 nt mRNA, was reconstructed on the basis of gene prediction and homology searches. It encodes codanin-1, a putative o-glycosylated protein of 1,226 amino acids, with no obvious transmembrane domains. Codanin-1 has a 150-residue amino-terminal domain with sequence similarity to collagens and two shorter segments that show weak similarities to the microtubule-associated proteins, MAP1B (neuraxin) and synapsin. These findings, and the cellular phenotype, suggest that codanin-1 may be involved in nuclear envelope integrity, conceivably related to microtubule attachments. The specific mechanisms by which codanin-1 underlies normal erythropoiesis remain to be elucidated.
authors.affiliation: Pediatric Hematology Laboratory, Felsenstein Research Center, Rabin Medical Center, Petah Tikva, Israel.
authors.forename: Orly
authors.initials: O
authors.lastname: Dgany
authors.forename: Nili
authors.initials: N
authors.lastname: Avidan
authors.forename: Jean
authors.initials: J
authors.lastname: Delaunay
authors.forename: Tatyana
authors.initials: T
authors.lastname: Krasnov
authors.forename: Lea
authors.initials: L
authors.lastname: Shalmon
authors.forename: Hanna
authors.initials: H
authors.lastname: Shalev
authors.forename: Tal
authors.initials: T
authors.lastname: Eidelitz-Markus
authors.forename: Joseph
authors.initials: J
authors.lastname: Kapelushnik
authors.forename: Daniel
authors.initials: D
authors.lastname: Cattan
authors.forename: Alexandre
authors.initials: A
authors.lastname: Pariente
authors.forename: Michel
authors.initials: M
authors.lastname: Tulliez
authors.forename: Aurore
authors.initials: A
authors.lastname: Crétien
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Schischmanoff
authors.forename: Achille
authors.initials: A
authors.lastname: Iolascon
authors.forename: Eithan
authors.initials: E
authors.lastname: Fibach
authors.forename: Ariel
authors.initials: A
authors.lastname: Koren
authors.forename: Jochen
authors.initials: J
authors.lastname: Rössler
authors.forename: Martine
authors.initials: M
authors.lastname: Le Merrer
authors.forename: Isaac
authors.initials: I
authors.lastname: Yaniv
authors.forename: Rina
authors.initials: R
authors.lastname: Zaizov
authors.forename: Edna
authors.initials: E
authors.lastname: Ben-Asher
authors.forename: Tsvyia
authors.initials: T
authors.lastname: Olender
authors.forename: Doron
authors.initials: D
authors.lastname: Lancet
authors.forename: Jacques S
authors.initials: JS
authors.lastname: Beckmann
authors.forename: Hannah
authors.initials: H
authors.lastname: Tamary
mesh_terms: D000595:Amino Acid Sequence; D000742:Anemia, Dyserythropoietic, Congenital / Q000235:genetics*; D001483:Base Sequence; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D003241:Consanguinity; D004920:Erythropoiesis; D005091:Exons / Q000235:genetics; D005260:Female; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D007557:Israel; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins; D010375:Pedigree; D010641:Phenotype; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: C470477:CDAN1 protein, human; D006023:Glycoproteins; D009687:Nuclear Proteins; D012333:RNA, Messenger