|
|
 Previous Article | Table of Contents | Next Article 
Blood, 1 June 2001, Vol. 97, No. 11, pp. 3327-3332
PLENARY PAPER
Genetic basis of hemolytic anemia caused by pyrimidine 5'
nucleotidase deficiency
Anthony M. Marinaki,
Emilia Escuredo,
John A. Duley,
H. Anne Simmonds,
Adolfo Amici,
Valeria Naponelli,
Giulio Magni,
Martin Seip,
Isaac Ben-Bassat,
Eric H. Harley,
Swee Lay Thein, and
David C. Rees
From the Purine Research Unit, Guy's Hospital; the
Department of Haematology, King's College Hospital, London; the
Department of Haematology, Royal Hallamshire Hospital, Sheffield,
United Kingdom; the Istituto di Biochimica, Facolta di Medicina,
Universita di Ancona, Italy; the Department of Pediatrics, The National
Hospital, Oslo, Norway; the Institute of Hematology, Chaim Sheba
Medical Center, Tel Hashomer, Israel; and the Department of Chemical
Pathology, University of Cape Town, South Africa.
Pyrimidine 5' nucleotidase (P5'N-1) deficiency is an autosomal
recessive condition causing hemolytic anemia characterized by marked
basophilic stippling and the accumulation of high concentrations of
pyrimidine nucleotides within the erythrocyte. It is implicated in the
anemia of lead poisoning and is possibly associated with learning
difficulties. Recently, a protein with P5'N-1 activity was analyzed and
a provisional complementary DNA (cDNA) sequence published. This
sequence was used to study 3 families with P5'N-1 deficiency. This
approach generated a genomic DNA sequence that was used to search
GenBank and identify the gene for P5'N-1. It is found on chromosome 7, consists of 10 exons with alternative splicing of exon 2, and produces
proteins 286 and 297 amino acids long. Three homozygous mutations were
identified in this gene in 4 subjects with P5'N-1 deficiency: codon 98 GAT GTT, AspVal (linked to a silent polymorphism codon 92, TACTAT), codon 177, CAATAA, Glntermination, and IVS9-1, GT.
The latter mutation results in the loss of exon 9 (201 bp) from the
cDNA. None of these mutations was found in 100 normal controls.
The DNA analysis was complicated by P5'N-1 pseudogenes found on
chromosomes 4 and 7. This study is the first description of the
structure and location of the P5'N-1 gene, and 3 mutations have been
identified in affected patients from separate kindreds.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
E. Bitto, C. A. Bingman, G. E. Wesenberg, J. G. McCoy, and G. N. Phillips Jr
Structure of Pyrimidine 5'-Nucleotidase Type 1: INSIGHT INTO MECHANISM OF ACTION AND INHIBITION DURING LEAD POISONING
J. Biol. Chem.,
July 21, 2006;
281(29):
20521 - 20529.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. R. Chiarelli, P. Bianchi, E. Fermo, A. Galizzi, P. Iadarola, A. Mattevi, A. Zanella, and G. Valentini
Functional analysis of pyrimidine 5'-nucleotidase mutants causing nonspherocytic hemolytic anemia
Blood,
April 15, 2005;
105(8):
3340 - 3345.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-M. Kim, H.-Y. Sohn, S. Y. Yoon, J.-H. Oh, J. O. Yang, J. H. Kim, K. S. Song, S.-M. Rho, H. S. Yoo, Y. S. Kim, et al.
Identification of Gastric Cancer-Related Genes Using a cDNA Microarray Containing Novel Expressed Sequence Tags Expressed in Gastric Cancer Cells
Clin. Cancer Res.,
January 15, 2005;
11(2):
473 - 482.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Bianchi and J. Spychala
Mammalian 5'-Nucleotidases
J. Biol. Chem.,
November 21, 2003;
278(47):
46195 - 46198.
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Balta, F. Gumruk, N. Akarsu, A. Gurgey, and C. Altay
Molecular characterization of Turkish patients with pyrimidine 5' nucleotidase-I deficiency
Blood,
September 1, 2003;
102(5):
1900 - 1903.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
