• Bao-sheng Zhu, Jing He, Jie Zhang, Xiao-hong Zeng, Jie Su, Xiang-hu Xu, Su-yun Li, Hong Chen, and Yin-hong Zhang.
• First People's Hospital of Yunnan Province, Kunming, China. bszhu@yahoo.cn
• Zhonghua Fu Chan Ke Za Zhi. 2012 Feb 1;47(2):85-9.

ObjectiveTo investigate mutation spectrums of α- and β-haemoglobin genes in thalassemia patients and carriers in Yunnan province, and to establish procedures on prenatal gene diagnosis.MethodsTotally 10 033 counseling couples and pregnant women, and 22 cases of children with moderate or severe thalassemia were recruited from 5 parts of Yunnan Province, middle, western, eastern, southern and northern areas, during July 2009 to July 2011. Medical records, including results of haemoglobin electrophoresis, blood routine examination, and gene diagnosis of subjects were collected and saved in an database in Excel software by the Key Laboratory for Birth Defects and Genetic Diseases. Using multiple gap-PCR and PCR-reversed dot blotting kits, DNA samples collected from 1077 cases of haematological positive thalassemia patients and carriers were tested to determine common mutations of the α- or β-haemoglobin genes. The codon regions of haemoglobin genes were sequenced by the Sanger sequencing in cases that the mutation tests were negative. Mutation spectrums of α- and β-haemoglobin genes were concluded. Prenatal gene diagnosis was offered to fetuses who had risk of thalassemia major.Results(1) In 1077 cases of haemological screen positive subjects, deletions and mutations of α-haemoglobin gene were tested in 119 subjects among 347 cases suspected as α-thalassemia patients and carriers. Five kinds of deletions and mutations on α-haemoglobin gene were found. In 104 subjects, four kinds of common deletions and mutations onα-haemoglobin gene were determined: --(SEA), -α(3.7), α(CS)α, -α(4.2). Other 14 subjects were double heterozygotes with haemoglobin H disease and severe α-thalassemia phenotypes. A rare mutation of insertion and deletion in α2 haemoglobin gene intron, α(301-24_301-23 indel), was found in one carrier subject. (2) In 1077 cases of haemological screen positive subjects, deletions and mutations of β-haemoglobin gene were tested in 297 subjects among 730 cases suspected as β-thalassemia patients and carriers. Sixteen kinds of β-haemoglobin gene mutations were found, including 7 cases of rare abnormal haemoglobinopathy patients with β-haemoglobin gene mutations. In one case with β(+) phenotype patient, the Codon 5(-CT) mutation at β-haemoglobin gene was found (firstly reported in China). (3) Three fetuses with high risks of α-thalassemia were accepted for prenatal diagnosis. One case of Hb Bart's hydrops syndrome fetus with the genotype --(SEA)/--(SEA), and one case of mild α-thalassemia fetus with the genotype α(CS)α/αα were found. Another one fetus was found with normal α-haemoglobin. In 6 fetuses accepted for prenatal diagnosis due to high risks of β-thalassemia, one case of β-thalassemia major with the genotype CD(17)(A→T)/-28(A→G) was found, 3 fetuses were heterozygote carriers, and 2 fetuses had normal genotypes without mutations found in their parents. Medical terminations for 2 fetuses with severe thalassemia were made according to the choice of pregnant women. Other 7 pregnancies continued to term. Anemia or growth retardation was not found in the 7 infants when following up after given-birth 6 to 12 months.ConclusionsThe mutation spectrums of α- and β-haemoglobin genes of thalassemia patients and carriers in Yunnan province are special, in which β-haemoglobin gene exits more polymorphism in the mutation spectrum. Carrier screening in pregnant women, and offering prenatal gene diagnosis to the high risk pregnancies should be an efficient strategy to prevent thalassemia major.

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