Molecular characterization of the PK-LR gene in sixteen pyruvate kinase-deficient patients

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

We studied the PK-LR gene in 16 unrelated patients with congenital haemolytic anaemia associated with erythrocyte pyruvate kinase deficiency. Fifteen different mutations were detected among the 28 mutated alleles identified: two deletions (del 1010G, del 1042-1044); one four nucleotide duplication (nt 1515-1518, GGTC); one splice site [IVS6(-2)t]; nine missense (991A, 1003A, 1151T, 1160G, 1181T, 1181A, 1456T 1483A, 1529A); and two nonsense (721T, 1675T) mutations. Eight of them [del 1010G, del 1042-1044, dupl 1515-1518, IVS6(-2)t, 1003A, 1160G, 1181T, 1181A] were novel. The deletion 1042-1044 causes the loss of Lys 348. Deletion 1010G and duplication 1515-1518 determine a frameshift and the creation of a stop codon at nucleotides 1019 and 1554 respectively. Mutation IVS6(-2)t leads to an alteration of the 5′ and 3′ splice site consensus sequence; the cDNA analysis shows a 67-bp deletion in the first part of exon 11 (del 1437-1503). All the four new missense mutations involve highly conserved amino acids. The most frequent mutation in Italy would appear to be 1456T. Correlation was made between mutations, biochemical characteristics of the enzyme and clinical course of the disease.

Original languageEnglish
Pages (from-to)43-48
Number of pages6
JournalBritish Journal of Haematology
Volume113
Issue number1
DOIs
Publication statusPublished - 2001

Fingerprint

Pyruvate Kinase
Mutation
RNA Splice Sites
Genes
Nucleotides
Congenital Hemolytic Anemia
Terminator Codon
Consensus Sequence
Missense Mutation
Italy
Exons
Complementary DNA
Alleles
Amino Acids
Enzymes

Keywords

  • Chronic haemolytic anaemia
  • Erythrocyte metabolism
  • Mutations
  • PK-LR gene
  • Pyruvate kinase deficiency

ASJC Scopus subject areas

  • Hematology

Cite this

@article{0f52236c7f7349279186b015783fb2d4,
title = "Molecular characterization of the PK-LR gene in sixteen pyruvate kinase-deficient patients",
abstract = "We studied the PK-LR gene in 16 unrelated patients with congenital haemolytic anaemia associated with erythrocyte pyruvate kinase deficiency. Fifteen different mutations were detected among the 28 mutated alleles identified: two deletions (del 1010G, del 1042-1044); one four nucleotide duplication (nt 1515-1518, GGTC); one splice site [IVS6(-2)t]; nine missense (991A, 1003A, 1151T, 1160G, 1181T, 1181A, 1456T 1483A, 1529A); and two nonsense (721T, 1675T) mutations. Eight of them [del 1010G, del 1042-1044, dupl 1515-1518, IVS6(-2)t, 1003A, 1160G, 1181T, 1181A] were novel. The deletion 1042-1044 causes the loss of Lys 348. Deletion 1010G and duplication 1515-1518 determine a frameshift and the creation of a stop codon at nucleotides 1019 and 1554 respectively. Mutation IVS6(-2)t leads to an alteration of the 5′ and 3′ splice site consensus sequence; the cDNA analysis shows a 67-bp deletion in the first part of exon 11 (del 1437-1503). All the four new missense mutations involve highly conserved amino acids. The most frequent mutation in Italy would appear to be 1456T. Correlation was made between mutations, biochemical characteristics of the enzyme and clinical course of the disease.",
keywords = "Chronic haemolytic anaemia, Erythrocyte metabolism, Mutations, PK-LR gene, Pyruvate kinase deficiency",
author = "Alberto Zanella and Paola Bianchi and Elisa Fermo and Alessandra Iurlo and Manuela Zappa and Cristina Vercellati and Carla Boschetti and Luciano Baronciani and Frederic Cotton",
year = "2001",
doi = "10.1046/j.1365-2141.2001.02711.x",
language = "English",
volume = "113",
pages = "43--48",
journal = "British Journal of Haematology",
issn = "0007-1048",
publisher = "John Wiley & Sons, Ltd (10.1111)",
number = "1",

}

TY - JOUR

T1 - Molecular characterization of the PK-LR gene in sixteen pyruvate kinase-deficient patients

AU - Zanella, Alberto

AU - Bianchi, Paola

AU - Fermo, Elisa

AU - Iurlo, Alessandra

AU - Zappa, Manuela

AU - Vercellati, Cristina

AU - Boschetti, Carla

AU - Baronciani, Luciano

AU - Cotton, Frederic

PY - 2001

Y1 - 2001

N2 - We studied the PK-LR gene in 16 unrelated patients with congenital haemolytic anaemia associated with erythrocyte pyruvate kinase deficiency. Fifteen different mutations were detected among the 28 mutated alleles identified: two deletions (del 1010G, del 1042-1044); one four nucleotide duplication (nt 1515-1518, GGTC); one splice site [IVS6(-2)t]; nine missense (991A, 1003A, 1151T, 1160G, 1181T, 1181A, 1456T 1483A, 1529A); and two nonsense (721T, 1675T) mutations. Eight of them [del 1010G, del 1042-1044, dupl 1515-1518, IVS6(-2)t, 1003A, 1160G, 1181T, 1181A] were novel. The deletion 1042-1044 causes the loss of Lys 348. Deletion 1010G and duplication 1515-1518 determine a frameshift and the creation of a stop codon at nucleotides 1019 and 1554 respectively. Mutation IVS6(-2)t leads to an alteration of the 5′ and 3′ splice site consensus sequence; the cDNA analysis shows a 67-bp deletion in the first part of exon 11 (del 1437-1503). All the four new missense mutations involve highly conserved amino acids. The most frequent mutation in Italy would appear to be 1456T. Correlation was made between mutations, biochemical characteristics of the enzyme and clinical course of the disease.

AB - We studied the PK-LR gene in 16 unrelated patients with congenital haemolytic anaemia associated with erythrocyte pyruvate kinase deficiency. Fifteen different mutations were detected among the 28 mutated alleles identified: two deletions (del 1010G, del 1042-1044); one four nucleotide duplication (nt 1515-1518, GGTC); one splice site [IVS6(-2)t]; nine missense (991A, 1003A, 1151T, 1160G, 1181T, 1181A, 1456T 1483A, 1529A); and two nonsense (721T, 1675T) mutations. Eight of them [del 1010G, del 1042-1044, dupl 1515-1518, IVS6(-2)t, 1003A, 1160G, 1181T, 1181A] were novel. The deletion 1042-1044 causes the loss of Lys 348. Deletion 1010G and duplication 1515-1518 determine a frameshift and the creation of a stop codon at nucleotides 1019 and 1554 respectively. Mutation IVS6(-2)t leads to an alteration of the 5′ and 3′ splice site consensus sequence; the cDNA analysis shows a 67-bp deletion in the first part of exon 11 (del 1437-1503). All the four new missense mutations involve highly conserved amino acids. The most frequent mutation in Italy would appear to be 1456T. Correlation was made between mutations, biochemical characteristics of the enzyme and clinical course of the disease.

KW - Chronic haemolytic anaemia

KW - Erythrocyte metabolism

KW - Mutations

KW - PK-LR gene

KW - Pyruvate kinase deficiency

UR - http://www.scopus.com/inward/record.url?scp=0035001459&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035001459&partnerID=8YFLogxK

U2 - 10.1046/j.1365-2141.2001.02711.x

DO - 10.1046/j.1365-2141.2001.02711.x

M3 - Article

C2 - 11328279

AN - SCOPUS:0035001459

VL - 113

SP - 43

EP - 48

JO - British Journal of Haematology

JF - British Journal of Haematology

SN - 0007-1048

IS - 1

ER -