First Report of Nondeletional Hb H Disease Caused by an α2-Globin Gene Mutation: HBA2: c.184A>T

In a previous study, we described a form of nondeletion alpha- thalassemia (alpha T Saudi alpha) found in subjects of Saudi Arabian origin. In the current study, using synthetic oligoprobe hybridization and restriction enzyme analysis, we have demonstrated that the molecular basis of alpha T Saudi alpha is due solely to a single base mutation (AATAAA----AATAAG) in the polyadenylation signal of the alpha 2 gene and that the frameshift mutation in codon 14 of the linked alpha 1 gene is the result of a cloning artefact. The alpha 2 polyadenylation signal mutation occurs in other Middle Eastern and the Mediterranean populations and is responsible for the clinical phenotype of Hb H disease in some Saudi Arabian individuals with five alpha genes (alpha T Saudi alpha/(alpha alpha alpha)T Saudi). Evidence suggests that the (alpha alpha alpha)T Saudi haplotype has arisen as a result of a recombination between two misaligned chromosomes bearing the alpha T Saudi alpha defect.

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Optimization of Pyrosequencing Method to Detect IVS1-NT5 ß-Globin Gene Mutation in ß-Thalassemia

International Journal of PharmTech Research ◽

10.20902/ijptr.2017.10114 ◽

2017 ◽

Vol 10 (2) ◽

pp. 96-102

Author(s):

Ani Melani Maskoen ◽

Dina Sofiana ◽

Lelani Reniarti

Keyword(s):

Gene Mutation ◽

Globin Gene ◽

Pyrosequencing Method

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Association of hereditary thrombocythemia and distal limb defects with a thrombopoietin gene mutation

Blood ◽

10.1182/blood-2009-04-217851 ◽

2009 ◽

Vol 114 (8) ◽

pp. 1655-1657 ◽

Cited By ~ 14

Author(s):

Claudio Graziano ◽

Simona Carone ◽

Emanuele Panza ◽

Flora Marino ◽

Pamela Magini ◽

...

Keyword(s):

Human Development ◽

Gene Mutation ◽

Autosomal Dominant ◽

Specific Gene ◽

Autosomal Dominant Disorder ◽

Distal Limb ◽

Limb Defects ◽

First Report

Abstract Hereditary thrombocythemia is a rare autosomal dominant disorder caused by mutations in either the thrombopoietin gene (TPO) or its receptor c-MPL. TPO mutations described so far lead to thrombopoietin overproduction through increased translation of m-RNA. Unilateral transverse reduction limb defects are usually sporadic and generally thought to be caused by vascular disruptions. Reports of inherited unilateral limb defects are extremely rare. In the present study, we describe a family with segregation of G185T TPO mutation in the 5′ UTR region in 4 subjects with thrombocythemia. Three of these patients also present congenital transverse limb defects. Association of these events gives a strong hint of the in vivo involvement of thrombopoietin in vasculogenesis, confirming the role of TPO in human development of the hemangioblast, the embryonic progenitor of the hematopoietic and endothelial lineages. This is the first report showing that vascular disruptions could be secondary to specific gene derangements.

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First Report of the 3'-Untranslated Region +1506 (A>C) [NM_000518.5: c.*32A>C] mutation on the β-Globin Gene in the Indian Population

Hemoglobin ◽

10.1080/03630269.2021.2011314 ◽

2021 ◽

pp. 1-4

Author(s):

Aditi Sen ◽

Venu Seenappa ◽

Prantar Chakrabarti ◽

Tuphan Kanti Dolai

Keyword(s):

Untranslated Region ◽

Indian Population ◽

Globin Gene ◽

First Report

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A first case of hemoglobin Castilla [Beta 32(B14) Leu>Arg; HBB: c.98T>G] associated with [IVS-I-1 (G>A); HBB:c.92+1G>A] mutation found in a Syrian betathalassemia patient

Thalassemia Reports ◽

10.4081/thal.2020.8396 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Ahmad Shoujaa ◽

Yasser Mukhalalaty ◽

Hossam Murad ◽

Faizeh Al-Quobaili

Keyword(s):

Molecular Analysis ◽

Clinical Case ◽

Globin Gene ◽

Thalassemia Major ◽

Beta Thalassemia ◽

Blood Transfusions ◽

Beta Globin ◽

First Report ◽

Beta Thalassemia Major ◽

First Case

Beta thalassemia (β-thal) is one of the most common worldwide inherited hemoglobinopathies. Proper identification and diagnosis of hemoglobin (Hb) variants provide a major challenge. In this report, we describe a 1-year-old boy, presented with the diagnosis of β-TM (beta thalassemia major), has received regular blood transfusions. The molecular analysis revealed the presence of rare Hb Castilla [Beta 32(B14) Leu>Arg; HBB: c.98T>G] variant associated with β0 [IVS-I-1 (G>A); AG^GTTGGT- >AGATTGGT beta0] (HBB:c.92+1G>A) Mutation in beta-globin (β-globin) gene. To our knowledge, this is the first report of Hb Castilla [Beta 32(B14) Leu>Arg] in ExonII of β-globin gene which were found in Syrian male proband. However, we should investigate abnormal hemoglobins in patients with beta thalassemia to determine whether they have involvement with β-thalassemia mutations in the clinical case of the patients or not.

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Hb DARTMOUTH [α66(E15)Leu → Pro (α2) (CTG → CCG)]: A NOVEL α2-GLOBIN GENE MUTATION ASSOCIATED WITH SEVERE NEONATAL ANEMIA WHEN INHERITED IN TRANS WITH SOUTHEAST ASIAN α-THALASSEMIA-1

Hemoglobin ◽

10.1081/hem-100107874 ◽

2001 ◽

Vol 25 (4) ◽

pp. 375-382 ◽

Cited By ~ 15

Author(s):

Kim L. McBride ◽

Karen Snow ◽

Kathleen S. Kubik ◽

Virgil F. Fairbanks ◽

James D. Hoyer ◽

...

Keyword(s):

Gene Mutation ◽

Globin Gene ◽

Southeast Asian ◽

In Trans

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Clinical Features and Molecular Analysis of Hb H Disease in Taiwan

BioMed Research International ◽

10.1155/2014/271070 ◽

2014 ◽

Vol 2014 ◽

pp. 1-5

Author(s):

Yu-Hua Chao ◽

Kang-Hsi Wu ◽

Han-Ping Wu ◽

Su-Ching Liu ◽

Ching-Tien Peng ◽

...

Keyword(s):

Clinical Features ◽

Globin Gene ◽

Clinical Manifestations ◽

Clinical Severity ◽

Blood Transfusions ◽

Limited Data ◽

Phenotype Correlation ◽

Younger Age ◽

Hb H Disease ◽

Thalassemia Mutation

Thalassemia is highly prevalent in Taiwan, but limited data are available about the association between genotypes and clinical manifestations in Taiwanese patients with Hb H disease. Here, we studied α-globin gene abnormalities and clinical features in Taiwanese patients with Hb H disease. Of the 90 patients, sixty-four (71.1%) were deletional and twenty-six (28.9%) were nondeletional Hb H disease. The (- -SEA) type ofα0-thalassemia mutation was detected in the majority of patients (>95%). The most common genotype was (- -SEA/-α3.7), followed by (- -SEA/αcsα). After further investigation of the genotype-phenotype correlation in 68 patients, we found that patients with nondeletional Hb H disease had more severe clinical features than those with deletional Hb H disease, including younger age at diagnosis, more requirement of blood transfusions, and larger proportion of patients with splenomegaly, hepatomegaly or jaundice. This is probably a consequence of the lower hemoglobin levels and the higher Hb H levels. The clinical severity was highly variable even among patients with an identical genotype, and the diversity was much more profound among patients with (- -/αcsα) genotype. Therefore, predicting the phenotype directly from the genotype in Hb H disease remains relatively difficult in Taiwan.

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