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Alpha0 thalassaemia as a result of a novel 11.1 kb deletion eliminating both of the duplicated alpha globin genes.

ABSTRACT: AIMS:To characterise a novel 11.1 kb deletion that eliminated both of the duplicated alpha globin genes, giving rise to a typical alpha0 thalassaemia phenotype in four carriers from a Chinese family. METHODS:Haematological investigations were carried out on all family members. The seven common forms of alpha thalassaemia were screened for by the polymerase chain reaction (PCR) and Southern blotting was used to analyse the alpha globin gene cluster. DNA sequence analysis of the entire alpha1 and alpha1 globin gene region was carried out and reverse transcription (RT)-PCR was used to investigate the transcription levels of the alpha and beta globin genes. RESULTS:The breakpoints were found to lie between coordinates 31695-31724 and 42846-42867 of the alpha globin gene cluster (NG_000006), with a total of about 11,135 nucleotides deleted. These sequences are involved in (CA)n repeats, suggesting a homologous recombination event. RT-PCR analysis gave a transcription level of the alpha globin gene in heterozygotes comparable with that of SEA deletion heterozygotes, confirming no output of alpha globin from the linked pair of alpha globin genes. The heterozygosity for this novel deletion was confirmed by PCR diagnosis in all four carriers from this family. CONCLUSIONS:This rare mutation constitutes an additional heterogeneous defect causing alpha thalassaemia in the Chinese population.

SUBMITTER: Jia SQ

PROVIDER: S-EPMC1770193 | biostudies-literature | 2004 Feb

REPOSITORIES: biostudies-literature

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Alpha0 thalassaemia as a result of a novel 11.1 kb deletion eliminating both of the duplicated alpha globin genes.

Jia S-Q SQ Li J J Mo Q-H QH Liao C C Li L-Y LY Xu X-M XM

Journal of clinical pathology 20040201 2

<h4>Aims</h4>To characterise a novel 11.1 kb deletion that eliminated both of the duplicated alpha globin genes, giving rise to a typical alpha0 thalassaemia phenotype in four carriers from a Chinese family.<h4>Methods</h4>Haematological investigations were carried out on all family members. The seven common forms of alpha thalassaemia were screened for by the polymerase chain reaction (PCR) and Southern blotting was used to analyse the alpha globin gene cluster. DNA sequence analysis of the ent ...[more]

PMID: 14747442

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Project description:Alpha-thalassaemia is inherited as an autosomal recessive disorder characterised by a microcytic hypochromic anaemia, and a clinical phenotype varying from almost asymptomatic to a lethal haemolytic anaemia.It is probably the most common monogenic gene disorder in the world and is especially frequent in Mediterranean countries, South-East Asia, Africa, the Middle East and in the Indian subcontinent. During the last few decades the incidence of alpha thalassaemia in North-European countries and Northern America has increased because of demographic changes. Compound heterozygotes and some homozygotes have a moderate to severe form of alpha thalassaemia called HbH disease. Hb Bart's hydrops foetalis is a lethal form in which no alpha-globin is synthesized. Alpha thalassaemia most frequently results from deletion of one or both alpha genes from the chromosome and can be classified according to its genotype/phenotype correlation. The normal complement of four functional alpha-globin genes may be decreased by 1, 2, 3 or all 4 copies of the genes, explaining the clinical variation and increasing severity of the disease. All affected individuals have a variable degree of anaemia (low Hb), reduced mean corpuscular haemoglobin (MCH/pg), reduced mean corpuscular volume (MCV/fl) and a normal/slightly reduced level of HbA2. Molecular analysis is usually required to confirm the haematological observations (especially in silent alpha-thalassaemia and alpha-thalassaemia trait). The predominant features in HbH disease are anaemia with variable amounts of HbH (0.8-40%). The type of mutation influences the clinical severity of HbH disease. The distinguishing features of the haemoglobin Bart's hydrops foetalis syndrome are the presence of Hb Bart's and the total absence of HbF. The mode of transmission of alpha thalassaemia is autosomal recessive. Genetic counselling is offered to couples at risk for HbH disease or haemoglobin Bart's Hydrops Foetalis Syndrome. Carriers of alpha+- or alpha0-thalassaemia alleles generally do not need treatment. HbH patients may require intermittent transfusion therapy especially during intercurrent illness. Most pregnancies in which the foetus is known to have the haemoglobin Bart's hydrops foetalis syndrome are terminated due to the increased risk of both maternal and foetal morbidity.

Dataset Information

Alpha0 thalassaemia as a result of a novel 11.1 kb deletion eliminating both of the duplicated alpha globin genes.

Publications

Alpha0 thalassaemia as a result of a novel 11.1 kb deletion eliminating both of the duplicated alpha globin genes.

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