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Molecular diagnosis of α‐thalassemia in a multiethnic population
Author(s) -
Gilad Oded,
Shemer Orna Steinberg,
Dgany Orly,
Krasnov Tanya,
Nevo Michal,
NoyLotan Sharon,
Rabinowicz Ron,
Amitai Nofar,
BenDor Shifra,
Yaniv Isaac,
Yacobovich Joanne,
Tamary Hannah
Publication year - 2017
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/ejh.12866
Subject(s) - multiplex ligation dependent probe amplification , thalassemia , point mutation , genetics , genotype , multiplex , population , biology , beta thalassemia , disease , molecular diagnostics , asymptomatic , mutation , genetic diagnosis , alpha thalassemia , medicine , gene , pathology , environmental health , exon
Objective α‐Thalassemia, one of the most common genetic diseases, is caused by deletions or point mutations affecting one to four α‐globin genes. Molecular diagnosis is important to prevent the most severe forms of the disease. However, the diagnosis of α‐thalassemia is complex due to a high variability of the genetic defects involved, with over 250 described mutations. We summarize herein the findings of genetic analyses of DNA samples referred to our laboratory for the molecular diagnosis of α‐thalassemia, along with a detailed clinical description. Methods We utilized a diagnostic algorithm including Gap‐ PCR , to detect known deletions, followed by sequencing of the α‐globin gene, to identify known and novel point mutations, and multiplex ligation‐dependent probe amplification ( MLPA ) for the diagnosis of rare or novel deletions. Results α‐Thalassemia was diagnosed in 662 of 975 samples referred to our laboratory. Most commonly found were deletions (75.3%, including two novel deletions previously described by us); point mutations comprised 25.4% of the cases, including five novel mutations. Our population included mostly Jews (of Ashkenazi and Sephardic origin) and Muslim Arabs, who presented with a higher rate of point mutations and hemoglobin H disease. Overall, we detected 53 different genotype combinations causing a spectrum of clinical phenotypes, from asymptomatic to severe anemia. Conclusion Our work constitutes the largest group of patients with α‐thalassemia originating in the Mediterranean whose clinical characteristics and molecular basis have been determined. We suggest a diagnostic algorithm that leads to an accurate molecular diagnosis in multiethnic populations.