Molecular Characterization of PK-LR Gene in Pyruvate Kinase–Deficient Italian Patients
| العنوان: | Molecular Characterization of PK-LR Gene in Pyruvate Kinase–Deficient Italian Patients |
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| المؤلفون: | Luciano Baronciani, Elena Bredi, Manuela Zappa, Paola Bianchi, Giovanni Pelissero, Alberto Zanella, Cristina Vercellati, Girolamo Sirchia, Fiorella Alfinito |
| المصدر: | Blood. 89:3847-3852 |
| بيانات النشر: | American Society of Hematology, 1997. |
| سنة النشر: | 1997 |
| مصطلحات موضوعية: | Genetics, Mutation, Point mutation, Nonsense mutation, Immunology, Cell Biology, Hematology, Biology, medicine.disease_cause, medicine.disease, Biochemistry, Stop codon, medicine, Missense mutation, Gene, Congenital hemolytic anemia, Pyruvate kinase deficiency |
| الوصف: | We studied the PK-LR gene in 15 unrelated Italian patients with congenital hemolytic anemia associated with erythrocyte pyruvate kinase (PK) deficiency. Fourteen different mutations were detected among 26 mutated alleles identified: a five-nucleotide (nt) deletion (227 to 231), two splice-site (1269C and IVS3(−2)c), 10 missense (514C, 787T, 823A, 993A, 994A, 1168A, 1456T, 1529A, 1552A, and 1594T) and one nonsense mutation(s) (721T). Eight of these (deletion 227-231, 1269C, IVS3(−2)c, 514C, 787T, 823A, 1168A, and 1552A) were novel. Moreover, a new polymorphic site was detected in the 3′ untranslated region of the mRNA (C/T, nucleotide 1738). The deletion 227-231 causes a stop codon after amino acid 77, probably resulting in an unstable gene product. Mutations 1269C and IVS3(−2)c lead to an alteration of the 5′ and 3′ splice-site consensus sequence, respectively; cDNA analysis failed to reveal any abnormal transcript, suggesting that these mutations generate an unstable mRNA that is rapidly degraded. Of the five new missense mutations, 823A (Gly275-Arg) and 1168A (Asp390-Asn) involve highly conserved amino acids, 514C (Glu172-Gln) and 1552A (Arg518-Ser), although found in less conserved regions, affect the balance of the electric charges of the protein. Mutation 787T (Gly263-Trp) is likely to determine strong modifications in the local structure of the molecule. The most frequent mutation in Italy appears to be 1456T (seven of 30 alleles), followed by 1529A (three of 30) and 994A (three of 30). A correlation was found between mutations, biochemical characteristics of the enzyme, and clinical course of the disease. |
| تدمد: | 1528-0020 0006-4971 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::66a25eeb15b9cfed2a89fd8e783af815 https://doi.org/10.1182/blood.v89.10.3847.3847_3847_3852 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....66a25eeb15b9cfed2a89fd8e783af815 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15280020 00064971 |
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