Hb H Disease Results from Compound Heterozygosity of - -SEA and -αMAL3.5 in a Chinese Family.

The α+-thal deletion of 3.557 kb (NG_000006.1: g.32745_36301del, -αMAL3.5), involving the entire α2-globin gene, was identified in a Chinese family by multiplex ligation-dependent probe amplification (MLPA) followed by gap-polymerase chain reaction (gap-PCR) and sequencing. The proband, a compound heterozygote for this mutant gene and the Southeast Asian (- -SEA; NG_000006.1: g.26264_45564del19301) deletion, had a phenotype of Hb H disease [hemoglobin (Hb) 7.6 g/dL, mean corpuscular volume (MCV) 60.0 fL, Hb H (ß4) 0.7%, Hb Bart's (γ4) 2.4% and Hb A2 1.1%]; one of her sisters with same genotype showed a similar phenotype. Another two family members, who were carriers of this mutant gene, had a hematological phenotype of a silent α-thal. The 5' and 3' breakpoints of this deletion are located at the Y2 and Y1 boxes, respectively, therefore, it probably originated from an unequal crossover between these two homologous boxes. This mutation constitutes an additional heterogeneous defect causing α-thal in the Chinese population and would be valuable for elucidating the arrangement in the human α-globin gene cluster.

Prevalence and molecular characterization of structural hemoglobin variants in the Dongguan region of Guangdong province, southern China.

The aim of the present study was to find the most prevalent structural hemoglobin (Hb) variants in southern China and to present hematological and molecular data of abnormal Hbs in the population from southern China. The type and frequency of structural Hb variants and their hematological and molecular characteristics were identified in 131 individuals from 30,848 unrelated partners who were referred to the prenatal clinic of Dongguan Maternal & Children Health Hospital, Dongguan, Guangdong, People's Republic of China (PRC) from 2011 to 2013. α-Globin or ß-globin chain variants were screened using a capillary electrophoresis (CE) system, and α-globin or ß-globin gene mutations were confirmed using sequencing techniques. The gene frequency of Hb variants was 0.4% (131/30,848). The most common α-globin variants were Hb Constant Spring (Hb CS, HBA2: c.427T > C) (0.2%), followed by Hb Q-Thailand (HBA1: c.223G > C) and Hb G-Honolulu (HBA2: c.91G > C). The most common ß-globin variant was Hb E (HBB: c.79G > A) (0.09%), followed by Hb New York (HBB: c.341T > A). Our results provide a detailed prevalence and molecular characterization of abnormal Hbs in the population of the Dongguan region. These findings have important implications for a region with a high frequency of α- and ß-thalassemias.

Delineation of the molecular basis of borderline hemoglobin A2 in Chinese individuals.

BACKGROUND: The "gray zone" of borderline hemoglobin A2 (Hb A2) may be present in a large section of the population, especially in countries where thalassemia is common. However, very little is currently known of the molecular basis of borderline Hb A2 in Chinese individuals. METHOD: In this study, we performed a comprehensive analysis of the globin genotypes and KLF1 gene mutations associated with borderline Hb A2 in 165 Chinese subjects. RESULT: Fifteen (9.1%) were positive for a molecular defect in the α-,ß-globin genes, of whom, α-thalassemia mutations and α-globin gene triplication were found in eleven cases, accounting for about 73.3% of these globin gene defects. Twenty (12.1%) were positive for a molecular defect in the KLF1 gene. Eight different mutations were identified, six of which are here reported for the first time. The most common is the G176AfsX179 mutation, accounting for 50% of the total. CONCLUSIONS: The molecular characterization of borderline Hb A2 in Chinese individuals is significantly different than in Italian population. Our data is conductive to provision of genetic counseling for Chinese individuals with borderline Hb A2.