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 language | English |
|---|---|
| Pages (from-to) | 43-48 |
| Number of pages | 6 |
| Journal | British Journal of Haematology |
| Volume | 113 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2001 |
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Keywords
- Chronic haemolytic anaemia
- Erythrocyte metabolism
- Mutations
- PK-LR gene
- Pyruvate kinase deficiency
ASJC Scopus subject areas
- Hematology
Cite this
Molecular characterization of the PK-LR gene in sixteen pyruvate kinase-deficient patients. / Zanella, Alberto; Bianchi, Paola; Fermo, Elisa; Iurlo, Alessandra; Zappa, Manuela; Vercellati, Cristina; Boschetti, Carla; Baronciani, Luciano; Cotton, Frederic.
In: British Journal of Haematology, Vol. 113, No. 1, 2001, p. 43-48.Research output: Contribution to journal › Article
}
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 -