IthaID: 237
Names and Sequences
| Functionality: | Globin gene causative mutation | Pathogenicity: | Pathogenic / Likely Pathogenic |
|---|---|---|---|
| Common Name: | CD 114 CTG>CCG [Leu>Pro] | HGVS Name: | HBB:c.344T>C |
| Hb Name: | Hb Durham-N.C. | Protein Info: | β 114(G16) Leu>Pro |
Context nucleotide sequence:
CTGGGCAACGTGCTGGTCTGTGTGC [C/T] GGCCCATCACTTTGGCAAAGAATTC (Strand: -)
Protein sequence:
MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVPAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH
Also known as: Hb Brescia
Comments: The rare Hb Durham-N.C. variant was presented in compound heterozygosity with the common IVS-I-110 (HBB: c.93-21G>A) variant, causing an early-onset severe β-Thalassaemia phenotype [PMID: 31456457]. Found in a heterozygous state in a Kurdish/Jew patient presenting with thalassaemia intermedia [PMID: 8980256]. Also reported in an Italian patient as a de novo mutation [PMID: 1301199].
We follow the HGVS sequence variant nomenclature and IUPAC standards.
Phenotype
| Hemoglobinopathy Group: | Thalassaemia and Structural Haemoglobinopathy |
|---|---|
| Hemoglobinopathy Subgroup: | β-thalassaemia, β-chain variant |
| Allele Phenotype: | Thalassaemia dominant Dominant |
| Stability: | Unstable |
| Oxygen Affinity: | N/A |
| Associated Phenotypes: |
Haemolytic anaemia [HP:0001878] Ineffective erythropoiesis [HP:0010972] |
Location
| Chromosome: | 11 |
|---|---|
| Locus: | NG_000007.3 |
| Locus Location: | 71918 |
| Size: | 1 bp |
| Located at: | β |
| Specific Location: | Exon 3 |
Other details
| Type of Mutation: | Point-Mutation(Substitution) |
|---|---|
| Effect on Gene/Protein Function: | Missense codons (Protein Structure) |
| Ethnic Origin: | US Irish, Italian, Irish, Russian, Sicilian, Kurdish Jew |
| Molecular mechanism: | Altered secondary structure |
| Inheritance: | Dominant |
| DNA Sequence Determined: | Yes |
In silico pathogenicity prediction
Frequencies
Publications / Origin
- Murru S, Poddie D, Sciarratta GV, Agosti S, Baffico M, Melevendi C, Pirastu M, Cao A, A novel beta-globin structural mutant, Hb Brescia (beta 114 Leu-Pro), causing a severe beta-thalassemia intermedia phenotype., Hum. Mutat., 1(2), 124-8, 1992
- Cürük MA, Molchanova TP, Postnikov YuV , Pobedimskaya DD, Liang R, Baysal E, Kolodey S, Smetanina NS, Tokarev YuN , Rumyantsev AG, Beta-thalassemia alleles and unstable hemoglobin types among Russian pediatric patients., American journal of hematology, 46(4), 329-32, 1994
- de Castro CM, Devlin B, Fleenor DE, Lee ME, Kaufman RE, A novel beta-globin mutation, beta Durham-NC [beta 114 Leu-->Pro], produces a dominant thalassemia-like phenotype., Blood, 83(4), 1109-16, 1994
- Rund D, Oron-Karni V, Filon D, Goldfarb A, Rachmilewitz E, Oppenheim A, Genetic analysis of beta-thalassemia intermedia in Israel: diversity of mechanisms and unpredictability of phenotype., Am. J. Hematol., 54(1), 16-22, 1997
- Cannata M, Cassarà F, Vinciguerra M, Licari P, Passarello C, Leto F, Lo Pinto C, Pitrolo L, Ganci R, Maggio A, Giambona A, Double Heterozygosity for Hb Durham-N.C. (: c.344T>C) [β114(G16)Leu→Pro] and the IVS-I-110 (: c.93-21G>A) Causing a Severe β-Thalassemia Phenotype., Hemoglobin, 43(3), 210-213, 2019