Molecular epidemiology, pathogenicity, and structural analysis of haemoglobin variants in the Yunnan province population of Southwestern China

Zhang, Jie; Yang, Yang; Yan, Yuanlong; Zeng, Xianying; Li, Dongmei; Chen, Hong; Su, Jie; Zhu, Baosheng

doi:10.1038/s41598-019-44793-0

Cited by 7 publications

(6 citation statements)

References 38 publications

(51 reference statements)

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“…The most common mutation was CD41/42 (‐TCTT), which was consistent with data from Guangdong and several nearby provinces 6,12,13,21,22 . In other provinces, such as Hunan, Yunnan and Fujian, IVS‐II‐654 (C>T) was the most common mutation, whilst CD41/42 (‐TCTT) was the second most common 23,24,25 . These studies indicated that the common and widespread mutations were similar across southern China, with diverse frequencies.…”

Section: Discussionsupporting

confidence: 83%

“…6,12,13,21,22 In other provinces, such as Hunan, Yunnan and Fujian, IVS-II-654 (C>T) was the most common mutation, whilst CD41/42 (-TCTT) was the second most common. 23,24,25 These studies indicated that the common and widespread mutations were similar across southern China, with diverse frequencies. The different distribution of β-globin mutations, across different geographical locations, reflects the heterogeneity of β-thalassemia.…”

Section: Hematological Parameters In Thalassemia Carriers Of Differen...mentioning

confidence: 95%

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Molecular spectrum of α‐ and β‐thalassemia among individuals of reproductive age in the Zhuhai region of southern China

Wang

Huang

Zhao

et al. 2023

Int J Lab Hematology

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Introduction Thalassemia is the most common monogenic disease in South and Southeast Asia. An accurate assessment of the relative frequency and composition of thalassemia mutations is important for the design of appropriate strategies to prevent the disease. In this study, we aimed to decode the molecular characterization of thalassemia mutations in Zhuhai region of southern China. Methods A total of 8048 individuals who were potential thalassemia carriers were enrolled. Gap‐polymerase chain reaction (Gap‐PCR) and reverse dot‐blot (RDB) hybridization methods were employed to detect common deletional and non‐deletional thalassemia mutations. Multiplex ligation dependent probe amplification (MLPA) and Sanger sequencing were used to analyze and verify rare and complex mutations. Results We diagnosed 3433 individuals as thalassemia carriers or patients. Of these, 2395 (69.76%) individuals with α‐thalassemia harbored 13 α‐globin gene mutations. The three most common α‐thalassemia mutations were ‐‐SEA (60.08%), ‐α3.7 (20.62%) and ‐α4.2 (9.25%). We diagnosed 903 (26.30%) individuals with β‐thalassemia and identified 20 β‐globin gene mutations, of which the three most frequent were CD41/42 (‐TCTT) (38.10%), IVS‐II‐654 (C>T) (23.69%) and TATAbox‐28 (A>G) (15.18%). In addition, we identified 15 rare thalassemia variants. We also summarized the association between the thalassemia genotype and hematological parameters, which demonstrated the broad phenotypic heterogeneity caused by globin gene mutations. Conclusion This is the first survey of thalassemia molecular epidemiology and hematological phenotype in Zhuhai region. It uncovered a high prevalence and complex molecular spectrum of thalassemia. These findings can be used as a basis for thalassemia diagnosis, counseling and prevention management.

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Section: Discussionsupporting

confidence: 83%

Section: Hematological Parameters In Thalassemia Carriers Of Differen...mentioning

confidence: 95%

Molecular spectrum of α‐ and β‐thalassemia among individuals of reproductive age in the Zhuhai region of southern China

Wang

Huang

Zhao

et al. 2023

Int J Lab Hematology

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“…According to the Iranome database, the HBD: c.394C>G variant has been observed in a Kurdish healthy individual in heterozygous form. Since the only report of this variant in the literature is related to Zhang et al's [21] study, it can be assumed that the present study is the second one to report this variant in the world and the first study to annotate it in Iran.…”

Section: Discussionmentioning

confidence: 84%

“…Zhang et al [21] reported p.Gln132Glu (HBD: c.394C>G) as a novel δ-globin variant in a healthy Chinese 35-year-old man in 2019 and named it Hb A2-Puer. The hematological and electrophoretic data related to this Hb variant in heterozygous state were as follows: Hb (g/dL) 16.1, MCV (fL) 85.2, MCH (pg) 29.0, Hb A (%) 97.4, Hb A 2 (%) 1.3, and Hb X (%) 1.4.…”

Section: Discussionmentioning

confidence: 99%

In silico prediction of HBD gene variants in the Iranian population

Moradi

Alibakhshi

Kazeminia

2021

Egypt J Med Hum Genet

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Background The quantification of hemoglobin A2 (Hb A2; α2δ2) is used as a valuable test to differentiate α- and ß-thal carriers in clinical laboratories. Therefore, the HBD (δ-globin) gene variants could result in reduced levels of Hb A2 and have implications for thalassemia screening programs. The aim of the present study was to predict the consequences of HBD gene variants identified in the Iranome project. Results The highest number of variants was in the Persian Gulf Islanders. The variants of p.Gln132Glu (HBD: c.394C>G), p.Gly17Arg (HBD: c.49G>C), p.Thr5Ile (HBD: c.14C>T), and p.Ala28Ser (HBD: c.82G>T) presented damage results in three or more prediction tools. In addition, it seems that the p.Gly30= (HBD: c.90C>T) decreases the use of authentic splice and, instead, creates a new donor splice site (DSS) or leads to the use of a cryptic DSS. Conclusions Most of these variants have been associated with a decrease in Hb A2 levels. Due to the high mutational diversity in the HBB gene in the Iranian population and the use of Hb A2 quantification to differentiate α- and ß-thal carriers among Iranian clinical laboratories, some attention should be taken to a possible co-inheritance of HBD gene variants to avoid the misdiagnosis of ß-thal carriers.

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“…The thalassaemias are characterised by absent or decreased production of normal haemoglobin. Whereas, the Hb variants are characterised by structural protein abnormalities in the globin chains, including α-globins, β-globins, δ-globins and γ-globins 3. To date, more than 1800 entries of variants have been registered in the Globin Gene Server, Hb var database 4.…”

Section: Introductionmentioning

confidence: 99%

Molecular characterisation of Hb Akron [β52 (D3) Asp→Val] combined with thalassaemia in a Chinese family

Wang

Shang

et al. 2022

J Clin Pathol

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AimsHb Akron (HBB:c.158A>T) is a rare β-chain variant and many characteristics about its clinical features still remain unclear. In this study, we aimed to explore the molecular and haematological characterisations of previously undescribed states for Hb Akron associated with different forms of thalassaemia.MethodsHaematology and genetic analysis were performed in 9 members from a Chinese Zhuang ethnic family.ResultsHb Akron in various combinations with β0-thalassaemia and α0-thalassaemia were identified and characterised. Simple heterozygote for Hb Akron is asymptomatic, while the compound heterozygotes of Hb Akron associated with the β0-thalassaemia mutation generates a more severe haematological phenotype than Hb Akron or β0-thalassaemia mutation seen in isolation. The specific peak of Hb Akron appears at Zone D (195–225 s) in the state of heterozygote and compound heterozygote on haemoglobin capillary electrophoresis device, and the reduction of Hb Akron level in heterozygotes is proportional to the degree of α-globin gene deficiency.ConclusionsWe have for the first time described the genetic and haematological characteristics of Hb Akron combined with different thalassaemia mutations, which will provide useful information for genetic counselling and prenatal diagnostic service of this mutation in a population with high prevalence of thalassaemia.

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Molecular epidemiology, pathogenicity, and structural analysis of haemoglobin variants in the Yunnan province population of Southwestern China

Cited by 7 publications

References 38 publications

Molecular spectrum of α‐ and β‐thalassemia among individuals of reproductive age in the Zhuhai region of southern China

Molecular spectrum of α‐ and β‐thalassemia among individuals of reproductive age in the Zhuhai region of southern China

In silico prediction of HBD gene variants in the Iranian population

Molecular characterisation of Hb Akron [β52 (D3) Asp→Val] combined with thalassaemia in a Chinese family

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