The Diverse Molecular Basis and Mild Clinical Picture of HbH Disease in Israel

Tamary, Hannah; Klinger, G; Shalmon, Lea; Kirschmann, H.; Koren, Ariel; Bennet, Michael; Zaizov, Rina

doi:10.1111/j.1749-6632.1998.tb10513.x

Cited by 8 publications

(8 citation statements)

References 8 publications

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“…Only one allele was an AATAAA!AATGAA transition, previously described as a T-Turkish a (24), also found in the Middle East (25) and Greece (24,26). Mild Hb H phenotypes in association with a T-Saudi a have been reported in patients from the UAE (21) and also in Iraqi Jews (28). The a T-Saudi a mutation was first described in this population by Yuregir et al (27) in 1992.…”

Section: Discussionmentioning

confidence: 86%

Molecular Basis of Hb H Disease in Southwest Iran

Yavarian¹,

Karimi²,

Zorai³

et al. 2005

LHEM

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Although alpha0-thalassemia (thal) defects are not very frequent in the Iranian population, Hb H disease does occur in the country. We have analyzed the alpha gene cluster of 13 patients showing the presence of Hb H to establish the molecular background of this disease in southwest Iran (Shiraz and Hormozgan provinces). Using gap-polymerase chain reaction (gap-PCR) and direct DNA sequencing we have found the --MED-I deletion, the polyadenylation signal (poly A) mutations alphaT-Saudi alpha and alphaT-Turkish alpha and Hb Constant Spring (Hb CS) in association with the common -alpha3.7 deletion. This study has revealed that: 1) at least six genotypes are responsible for Hb H disease in the area: .-alpha3.7/ --MED-I; -alpha3.7/alphaT-Saudi alpha; alphaT-Saudi alpha/alphaT-Saudi alpha; alphaCSalpha/--MED-I; --MED-I/alphaT-Turkish alpha; and the atypical forms of Hb H disease -alpha3.7/alphaCSalpha. 2) The molecular background of Hb H disease in the southwest area of Iran is more similar to the Mediterranean type than to the Southeast Asian. 3) Hb Bart's hydrops fetalis syndrome and mild, intermediate or severe postnatal Hb H disease conditions can be expected, but at a relatively low incidence. 4) The diagnostic flowchart for patients with microcytic hypochromic anemia should include iron deficiency, beta-thal, alpha+- and alpha0-thal analyses.

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Section: Discussionmentioning

confidence: 86%

Molecular Basis of Hb H Disease in Southwest Iran

Yavarian¹,

Karimi²,

Zorai³

et al. 2005

LHEM

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“…Such pregnancies are accompanied by increased risks of maternal complications. The loss of three α‐globin genes in the compound heterozygotes of double gene and single gene deletions (−α/− −) or in the compound heterozygotes of a double gene deletion and a non‐deletional α‐thalassaemia mutation (− −/α T α) result in a less severe condition known as haemoglobin H (HbH) disease which causes chronic haemolytic anaemia of variable severity in children and adults (Galanello et al , 1992); (Tamary et al , 1998).…”

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confidence: 99%

Determination of the breakpoint and molecular diagnosis of a common α‐thalassaemia‐1 deletion in the Indian population

Shaji¹,

Eunice²,

Baidya

et al. 2003

Br J Haematol

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Summary. The previously described South African type a-thalassaemia-1 mutation was identified in Indian HbH patients using a polymerase chain reaction (PCR) strategy. A multiplex PCR assay was devised to detect heterozygotes and homozygotes. This a-thalassaemia-1 mutation was found to be the commonest determinant causing HbH disease in this population. In one family this mutation was found in combination with a novel splice donor mutation a2 IVS I-1 (G fi A). Characterization of the breakpoint junction sequence revealed, in addition to a 23 kb deletion, that there was an addition of 160 bp bridging the breakpoints. Similar to other deletions in the a-globin gene cluster, there is an Alu repeat-mediated mechanism for the origin of the deletion. Keywords: a-thalassaemia, PCR, India, AluThe a-thalassaemias are genetic defects characterized by the decrease or complete suppression of synthesis of the a-globin polypeptide chains of haemoglobin. They are the most common single-gene diseases in the world. The a-globin genes are duplicated (a1 and a2) and located within the a gene cluster f2)wf1)wa2)wa1)a2)a1)h1 on the distal short arm region of chromosome 16 (Higgs et al, 1989). This cluster contains four genes and three pseudogenes. Deletions of one ()a) or both () ) )) of these cis-linked genes are the most common causes of the a-thalassaemias. Around 25 different two-gene cis deletions () )) and eight single-gene deletions ()a)

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“…There have been several mutational surveys of Hb H disease patients in various regions of the Mediterranean basin [7,[9][10][11][12][13] and southeast Asia [16][17][18]. As is the case for ␤-thalassemia, each population group is characterized by a relatively small number of ␣-thalassemia determinants and Hb H disease genotypes.…”

Section: Introductionmentioning

confidence: 99%

“…In general, however, the loss or inactivation of three ␣-globin genes (-␣/− or ␣ T ␣/− or ␣␣ T /−) results in a less severe condition known as hemoglobin H (Hb H) disease. Hb H disease can also be caused by homozygosity for nondeletion ␣-thalassemia mutations or unstable ␣-chain variants [7,8].…”

Section: Introductionmentioning

confidence: 99%