Thalassemia in Western Australia: 11 novel deletions characterized by Multiplex Ligation-dependent Probe Amplification

The number of immigrants in Western Australia from many different areas where hemoglobinopathies are endemic has increased dramatically since the 1970s. Therefore, many different thalassemia mutations have been introduced in the country, which add a technological diagnostic problem to the serious bu...

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Bibliographic Details
Published in:Blood cells, molecules, & diseases molecules, & diseases, 2010-03, Vol.44 (3), p.146-151
Main Authors: Phylipsen, Marion, Prior, John F., Lim, Erna, Lingam, Neela, Vogelaar, Ingrid P., Giordano, Piero C., Finlayson, Jill, Harteveld, Cornelis L.
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
alpha-Globins - genetics
Australia - ethnology
Base Sequence
beta-Globins - genetics
Child
Child, Preschool
Deletion breakpoint characterization
Female
Genetic Testing
Humans
Male
Middle Aged
MLPA
Molecular Sequence Data
Multigene Family
Sequence Deletion
Thalassemia
Thalassemia - diagnosis
Thalassemia - ethnology
Thalassemia - genetics
Young Adult
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Summary:The number of immigrants in Western Australia from many different areas where hemoglobinopathies are endemic has increased dramatically since the 1970s. Therefore, many different thalassemia mutations have been introduced in the country, which add a technological diagnostic problem to the serious burden of hemoglobinopathy management and to public health care. Recently, we have developed a rapid and simple technique based on Multiplex Ligation-dependent Probe Amplification to detect deletions causing α-and β-thalassemia, δβ-thalassemia and Hereditary Persistence of Fetal Hemoglobin. A screening for (unknown) deletions was performed in a cohort of patients of different ethnic backgrounds preselected for their thalassemia phenotype, in which common deletions and point mutations were excluded. Out of 37 cases suspected to carry a deletion, 27 were found to carry 17 different deletion types of which 6 causing α-thalassemia and 5 causing β-thalassemia were novel. For 3 of the deletions, we have been able to characterize the exact breakpoint sequences by long-range PCR and direct sequencing. These results show that MLPA is a suitable technology to detect unknown and uncommon deletions. These could represent a diagnostic problem when offering prevention to couples at risk presenting with unclear phenotypes and might result in a serious fetal problem when the deletion involves embryonic genes.
ISSN:1079-9796
1096-0961
DOI:10.1016/j.bcmd.2009.12.011