Molecular analysis of complex cases of alpha- and beta-thalassemia in Mexican mestizo patients with microcytosis and hypochromia reveals two novel alpha(0)-thalassemia deletions --(Mex1) and --(Mex2)

作者：De La Cruz Salcedo E I; Ibarra B; Rizo De La Torre L C; Sanchez Lopez J Y; Gonzalez Mercado A; Harteveld C L; Perea Diaz F J

来源：International Journal of Laboratory Hematology, 2016, 38(5): 535-542.

DOI：10.1111/ijlh.12536

• complex - and -thalassemia genotypes
• microcytosis
• alpha-globin deletion

IntroductionAlpha-thalassemia (-thal) is a common monogenic disorder worldwide. In mixed ethnic populations, -thal and beta-thalassemia (-thal) can be expected, sometimes giving complex phenotypes, which without molecular analysis are not easily explained. We performed the molecular identification of - and -thal alleles in 51 Mexican patients with microcytosis, hypochromia, and normal or low levels of HbA(2).
MethodsCommon deletional alleles (-(3.7), -(4.2), - -(SEA), - -(MED), - -(FIL), - -(THAI), -(20.5)) and -triplication were studied by gap-PCR and nondeletional alleles ((IVSI(-5nt)), (NcoI)(2), (NcoI)(1)) by ARMS. -thal alleles Cd39 (C>T), IVS1:1 (G>A), IVS1:110 (G>A), and Spanish -thal were also investigated. DNA sequencing was performed on HBA2, HBA1, and HBB genes. Negative samples were subjected to MLPA.
ResultsIn 35 subjects, we identified the mutations, -(3.7), - -(SEA), - -(FIL), (IVSI(-5nt)), and (anti3.7) and two novel deletion alleles - -(Mex1) (6.8-8.9 kb) and - -(Mex2) (77.6-135.7 kb). Four individuals also had a -thal allele (Cd39/IVS1:110). No -thal alleles were observed in 16 subjects, but three had a -thal mutation Cd39, IVS1:110, and Spanish -thal.
Conclusion-thal is relatively common in Mexican patients, the combination with -thal is sometimes unexpected, and this underlines the importance of performing molecular analysis for both - and -genes defects in patients showing microcytic hypochromic anemia.

• 出版日期2016-10