An alpha-thalassemia phenotype in a Dutch Hindustani, caused by a new point mutation that creates an alternative splice donor site in the first exon of the alpha2-globin gene. 2004

Cornelis L Harteveld, and Pierre W Wijermans, and Peter van Delft, and Ellen Rasp, and Hans L Haak, and Piero C Giordano
Hemoglobinopathies Laboratory, Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands. C.L.Harteveld@lumc.nl

The proband is an elderly woman (79 years of age) of Surinamese-Hindustani origin, suspected of being a carrier of a nondeletional alpha-thalassemia (thal) because of a moderate microcytic hypochromic anemia at normal ferritin levels and in the absence of any other alpha-thal deletions. Sequence analysis revealed a silent mutation (GGC-->GGT) at codon 22 of the alpha2-globin gene. This mutation generates a splice donor site consensus sequence (GGTGAG) between codons 22 and 23. The abnormally spliced mRNA leads to a premature termination between codons 48 and 49. The presence of a downstream intron may induce the intracellular degradation of the affected mRNA, a pathway known as nonsense mediated decay (NMD), and this explains the alpha(+)-thal phenotype observed in the patient. The codon 22 (GGC-->GGT) transition described in this report is the first mutation creating a splice donor site in one of the alpha-globin genes.

UI MeSH Term Description Entries
D010443 Peptide Chain Termination, Translational A process of GENETIC TRANSLATION whereby the terminal amino acid is added to a lengthening polypeptide. This termination process is signaled from the MESSENGER RNA, by one of three termination codons (CODON, TERMINATOR) that immediately follows the last amino acid-specifying CODON. Chain Termination, Peptide, Translational,Protein Biosynthesis Termination,Protein Chain Termination, Translational,Protein Translation Termination,Translation Termination, Genetic,Translation Termination, Protein,Translational Peptide Chain Termination,Translational Termination, Protein,Biosynthesis Termination, Protein,Genetic Translation Termination,Protein Translational Termination,Termination, Genetic Translation,Termination, Protein Biosynthesis,Termination, Protein Translation,Termination, Protein Translational
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly
D000747 Anemia, Hypochromic Anemia characterized by a decrease in the ratio of the weight of hemoglobin to the volume of the erythrocyte, i.e., the mean corpuscular hemoglobin concentration is less than normal. The individual cells contain less hemoglobin than they could have under optimal conditions. Hypochromic anemia may be caused by iron deficiency from a low iron intake, diminished iron absorption, or excessive iron loss. It can also be caused by infections or other diseases, therapeutic drugs, lead poisoning, and other conditions. (Stedman, 25th ed; from Miale, Laboratory Medicine: Hematology, 6th ed, p393) Chlorosis,Anemias, Hypochromic,Chloroses,Hypochromic Anemia,Hypochromic Anemias
D012326 RNA Splicing The ultimate exclusion of nonsense sequences or intervening sequences (introns) before the final RNA transcript is sent to the cytoplasm. RNA, Messenger, Splicing,Splicing, RNA,RNA Splicings,Splicings, RNA
D017085 alpha-Thalassemia A disorder characterized by reduced synthesis of the alpha chains of hemoglobin. The severity of this condition can vary from mild anemia to death, depending on the number of genes deleted. Hemoglobin H Disease,Thalassemia-alpha,A-Thalassemia,Alpha Thalassemia,Disease, Hemoglobin H,Thalassemia alpha,Thalassemia, Alpha,alpha-Thalassemias
D017354 Point Mutation A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. Mutation, Point,Mutations, Point,Point Mutations
D018388 Codon, Terminator Any codon that signals the termination of genetic translation (TRANSLATION, GENETIC). PEPTIDE TERMINATION FACTORS bind to the stop codon and trigger the hydrolysis of the aminoacyl bond connecting the completed polypeptide to the tRNA. Terminator codons do not specify amino acids. Amber Stop Codon,Codon, Amber Stop,Codon, Ochre Stop,Codon, Opal Stop,Codon, Stop,Stop Codon,Terminator Codon,Amber Codon,Amber Terminator Codon,Codon, Termination,Ochre Codon,Ochre Stop Codon,Opal Codon,Opal Stop Codon,Stop Codon UAA,Stop Codon UAG,Stop Codon UGA,Stop Signal, Translation,TAA Codon,TAG Codon,TGA Codon,UAA Codon,UAA Stop Codon,UAG Codon,UAG Stop Codon,UGA Codon,UGA Stop Codon,Amber Codons,Amber Stop Codons,Amber Terminator Codons,Codon UAA, Stop,Codon UAG, Stop,Codon UGA, Stop,Codon, Amber,Codon, Amber Terminator,Codon, Ochre,Codon, Opal,Codon, TAA,Codon, TAG,Codon, TGA,Codon, UAA,Codon, UAA Stop,Codon, UAG,Codon, UAG Stop,Codon, UGA,Codon, UGA Stop,Codons, Amber,Codons, Amber Stop,Codons, Amber Terminator,Codons, Ochre,Codons, Ochre Stop,Codons, Opal,Codons, Opal Stop,Codons, Stop,Codons, TAA,Codons, TAG,Codons, TGA,Codons, Termination,Codons, Terminator,Codons, UAA,Codons, UAA Stop,Codons, UAG,Codons, UAG Stop,Codons, UGA,Codons, UGA Stop,Ochre Codons,Ochre Stop Codons,Opal Codons,Opal Stop Codons,Stop Codon UGAs,Stop Codon, Amber,Stop Codon, Ochre,Stop Codon, Opal,Stop Codon, UAA,Stop Codon, UAG,Stop Codon, UGA,Stop Codons,Stop Codons, Amber,Stop Codons, Ochre,Stop Codons, Opal,Stop Codons, UAA,Stop Codons, UAG,Stop Codons, UGA,Stop Signals, Translation,TAA Codons,TAG Codons,TGA Codons,Termination Codon,Termination Codons,Terminator Codon, Amber,Terminator Codons,Terminator Codons, Amber,Translation Stop Signal,Translation Stop Signals,UAA Codons,UAA Stop Codons,UAA, Stop Codon,UAG Codons,UAG Stop Codons,UAG, Stop Codon,UGA Codons,UGA Stop Codons,UGA, Stop Codon
D020871 RNA Stability The extent to which an RNA molecule retains its structural integrity and resists degradation by RNASE, and base-catalyzed HYDROLYSIS, under changing in vivo or in vitro conditions. RNA Decay,mRNA Decay,mRNA Transcript Degradation,RNA Degradation,RNA Instability,mRNA Degradation,mRNA Instability,mRNA Stability,Decay, RNA,Decay, mRNA,Degradation, RNA,Degradation, mRNA,Degradation, mRNA Transcript,Instability, RNA,Instability, mRNA,Stability, RNA,Stability, mRNA,Transcript Degradation, mRNA

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