Localization of the Gene for Congenital Dyserythropoietic Anemia Type I to a &lt;1-cM Interval on Chromosome 15q15.1-15.3

Tamary, Hannah; Shalmon, Lea; Shalev, Hanna; Halil, Albudar; Dobrushin, Dina; Ashkenazi, Noga; Zoldan, Meira; Resnitzky, P; Korostishevsky, Michael; Bonné‐Tamir, Batsheva; Zaizov, Rina

doi:10.1086/301834

Cited by 58 publications

(32 citation statements)

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“…As a result of the perfect cosegregation of these additional features with their CDAI status, these patients were meticulously examined for the possible involvement of chromosome 15 in their condition. 15 Detailed molecular analysis of this family's DNA samples revealed a B70 kb deletion in chromosome 15q15, removing part of the CATSPER2 gene, and suggesting the importance of this gene for sperm motility in humans.…”

Section: Introductionmentioning

confidence: 88%

“…In the course of positional cloning of the Congenital Dyserythropoietic Anemia type I (CDAI) gene [MIM 224120], 14 which was previously localized to chromosome 15q15.1 -15.3, 15 we examined a family of French origin, in which the clinical and hematological features of the propositus (II-2, Figure 1a) and of his two affected brothers were compatible with CDAI (Table 1). However, unlike other CDAI patients, the brothers suffered also from sensorineural deafness, and a severe reduction in the percentage of motile spermatozoa in their ejaculates ( Table 1).…”

Section: Introductionmentioning

confidence: 99%

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CATSPER2, a human autosomal nonsyndromic male infertility gene

et al. 2003

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Section: Introductionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

CATSPER2, a human autosomal nonsyndromic male infertility gene

et al. 2003

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“…[7][8][9] A cohort of 45 Israeli Bedouin patients with CDA I enabled us to map the disease gene to chromosome 15, between markers D15S779 and D15S778, and subsequently to clone the CDAN1 gene. 10,11 The CDAN1 gene, with its 28 exons, spans 15 kb of genomic DNA and encodes a 4738-nucleotide-long mRNA. Northern blot analysis revealed that the gene is ubiquitously expressed.…”

Section: Introductionmentioning

confidence: 99%

Codanin-1, the protein encoded by the gene mutated in congenital dyserythropoietic anemia type I (CDAN1), is cell cycle-regulated

Noy-Lotan

Dgany²,

Lahmi³

et al. 2009

Haematologica

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BackgroundCongenital dyserythropoietic anemia type I is an inherited autosomal recessive macrocytic anemia associated with ineffective erythropoiesis and the development of secondary hemochromatosis. Distinct erythroid precursors with internuclear chromatin bridges and spongy heterochromatin are pathognomonic for the disease. The mutated gene (CDAN1) encodes a ubiquitously expressed protein of unknown function, codanin-1. Based on the morphological features of congenital dyserythropoietic anemia type I erythroblasts and data on a role in cell cycle progression of codanin-1 homolog in Drosophila we investigated the cellular localization and possible involvement of codanin-1 during the cell cycle. Design and MethodsCodanin-1 localization was studied by immunofluorescence and immune electron microscopy. Cell cycle expression of codanin-1 was evaluated using synchronized HeLa cells. E2F proteins are the main regulator of G1/S transition. An E2F1-inducible cell line (U20S-ER-E2F1) enabled us to study codanin-1 expression following ectopic E2F1 induction. Direct binding of E2F1 to codanin-1 promoter was assessed by chromatin immunoprecipitation. We used a luciferase-reporter plasmid to study activation of CDAN1 transcription by E2F1. ResultsWe localized codanin-1 to heterochromatin in interphase cells. During the cell cycle, high levels of codanin-1 were observed in the S phase. At mitosis, codanin-1 underwent phosphorylation, which coincided with its exclusion from condensed chromosomes. The proximal CDAN1 gene promoter region, containing five putative E2F binding sites, was found to be a direct target of E2F1. ConclusionsTaken together, these data suggest that codanin-1 is a cell cycle-regulated protein active in the S phase. The exact role of codanin-1 during the S phase remains to be determined. Nevertheless this represents the first step towards understanding the function of the proteins involved in congenital dyserythropoietic anemia.Key words: codanin-1, cell cycle, heterochromatin, E2F.Citation: Dgany O, Lahmi R, Marcoux N, Krasnov T, Yissachar N, Ginsberg D, Motro B, Resnitzky P, Yaniv I, Kupfer GM, the ABSTRACT© F e r r a t a S t o r t i F o u n d a t i o n S. Noy-Lotan et al.

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“…52 The CDAN1 gene was successively cloned with 28 exons spanning 15 Kb and encoding a protein named codanin-1. In unrelated patients of European, Bedouin and Asian origin, different point mutations were detected.…”

Section: Cda Type Imentioning

confidence: 99%

Clinical aspects and pathogenesis of congenital dyserythropoietic anemias: from morphology to molecular approach

2012

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Congenital dyserythropoietic anemias belong to a group of inherited conditions characterized by a maturation arrest during erythropoiesis with a reduced reticulocyte production in contrast with erythroid hyperplasia in bone marrow. The latter shows specific morphological abnormalities that allowed for a morphological classification of these conditions mainly represented by congenital dyserythropoietic anemias types I and II. The identification of their causative genes provided evidence that these conditions have different molecular mechanisms that induce abnormal cell maturation and division. Some altered proteins seem to be involved in the chromatin assembly, such as codanin-1 in congenital dyserythropoietic anemia I. The gene involved in congenital dyserythropoietic anemia II, the most frequent form, is SEC23B. This condition seems to belong to a group of diseases attributable to defects in the transport of newly synthesized proteins from endoplasmic reticulum to the Golgi. This review will analyze recent insights in congenital dyserythropoietic anemias types I and II. It will also attempt to clarify the relationship between mutations in causative genes and the clinical phenotype of these conditions. Key words: dyserythropoiesis, congenital dyserythropoietic anemia, red blood cells, inherited anemias.Citation: Iolascon A, Esposito MR, and Russo R. Clinical aspects and pathogenesis of congenital dyserythropoietic anemias: from morphology to molecular approach. Haematologica 2012;97(12): 1786-1794. doi:10.3324/haematol.2012 This is an open-access paper. ABSTRACT © F e r r a t a S t o r t i F o u n d a t i o nto distinguish without molecular evaluation. 7,8 Recent identification of several causative genes could help reclassify these disorders (Table 1). Variant forms are very rare and this, up to now, has compromised further molecular studies. Linkage studies had previously been the main tool to clarify the genetics of Mendelian disorders; however, extremely rare disorders or sporadic cases caused by de novo variants are not appropriate for this type of study design. Exome sequencing is now becoming technically feasible and more cost-effective due to the recent advances in high-throughput sequence capture methods and next-generation sequencing technologies that have offered new opportunities for research into Mendelian disorders. 9 We suggest that the use of these new technologies will lead to the identification of new causative genes in CDA variants in the near future. In particular, this review will deal with new insights on the two most frequent forms of CDAs: types I and II. Epidemiology of CDAsUntil December 2011, 712 cases from 614 families were included in the German CDA Registry, 10,11 whereas 206Clinical aspects and pathogenesis of CDAs haematologica | 2012; 97 (12) 1787 © F e r r a t a S t o r t i F o u n d a t i o ncases from 183 families were enrolled in the Italian CDA registry (A Iolascon, unpublished data, 2011 Although CDA II patients are to be found right across the Italian peninsula, the maj...

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Localization of the Gene for Congenital Dyserythropoietic Anemia Type I to a <1-cM Interval on Chromosome 15q15.1-15.3

Cited by 58 publications

References 14 publications

CATSPER2, a human autosomal nonsyndromic male infertility gene

CATSPER2, a human autosomal nonsyndromic male infertility gene

Codanin-1, the protein encoded by the gene mutated in congenital dyserythropoietic anemia type I (CDAN1), is cell cycle-regulated

Clinical aspects and pathogenesis of congenital dyserythropoietic anemias: from morphology to molecular approach

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