title: Thalassemia in Western Australia: 11 novel deletions characterized by Multiplex Ligation-dependent Probe Amplification.
abstract: 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 alpha-and beta-thalassemia, deltabeta-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 alpha-thalassemia and 5 causing beta-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.
authors.affiliation: Department of Human and Clinical Genetics, Leiden University Medical Center, The Netherlands. m.phylipsen@lumc.nl
authors.forename: Marion
authors.initials: M
authors.lastname: Phylipsen
authors.forename: John F
authors.initials: JF
authors.lastname: Prior
authors.forename: Erna
authors.initials: E
authors.lastname: Lim
authors.forename: Neela
authors.initials: N
authors.lastname: Lingam
authors.forename: Ingrid P
authors.initials: IP
authors.lastname: Vogelaar
authors.forename: Piero C
authors.initials: PC
authors.lastname: Giordano
authors.forename: Jill
authors.initials: J
authors.lastname: Finlayson
authors.forename: Cornelis L
authors.initials: CL
authors.lastname: Harteveld
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001315:Australia / Q000208:ethnology; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D005810:Multigene Family; D017384:Sequence Deletion; D013789:Thalassemia / Q000175:diagnosis / Q000208:ethnology* / Q000235:genetics*; D055815:Young Adult; D055542:alpha-Globins / Q000235:genetics*; D055544:beta-Globins / Q000235:genetics*
chemical_list: D055542:alpha-Globins; D055544:beta-Globins