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, Asp→Val (linked to a silent polymorphism codon 92, TAC→TAT), codon 177, CAA→TAA, Gln→termination, and IVS9-1, G→T. 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. © 2001 by The American Society of Hematology.

Genetic basis of hemolytic anemia caused by pyrimidine 5′ nucleotidase deficiency / Marinaki, A. M.; Escuredo, E.; Duley, J. A.; Anne Simmonds, H.; Amici, A.; Naponelli, V.; Magni, G.; Seip, M.; Ben-Bassat, I.; Harley, E. H.; Thein, S. L.; Rees, D. C.. - In: BLOOD. - ISSN 0006-4971. - 97:11(2001), pp. 3327-3332. [10.1182/blood.V97.11.3327]

Genetic basis of hemolytic anemia caused by pyrimidine 5′ nucleotidase deficiency

Naponelli V.;
2001

Abstract

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, Asp→Val (linked to a silent polymorphism codon 92, TAC→TAT), codon 177, CAA→TAA, Gln→termination, and IVS9-1, G→T. 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. © 2001 by The American Society of Hematology.
Genetic basis of hemolytic anemia caused by pyrimidine 5′ nucleotidase deficiency / Marinaki, A. M.; Escuredo, E.; Duley, J. A.; Anne Simmonds, H.; Amici, A.; Naponelli, V.; Magni, G.; Seip, M.; Ben-Bassat, I.; Harley, E. H.; Thein, S. L.; Rees, D. C.. - In: BLOOD. - ISSN 0006-4971. - 97:11(2001), pp. 3327-3332. [10.1182/blood.V97.11.3327]
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11381/2868816
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 49
  • ???jsp.display-item.citation.isi??? 42
social impact