Epidemiological Survey of Hemoglobinopathies Based on Next-Generation Sequencing Platform in Hunan Province, China.

Objective: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and ß-globin gene mutations in Hunan Province. Methods: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. Results: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for ß-thalassemia, and 0.12% for both α- and ß-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and ß-thalassemia was -α 3.7/αα (50.23%) and ß IVS-II-654/ß N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six ß-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. Conclusion: Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.

Assessment of orthodontic treatment needs in patients with ß-thalassemia major and sickle cell disease.

Patients suffering from hemoglobinopathies may suffer from pathogic dental and orofacial features. This study aimed to assess the prevalence of malocclusion and the need for orthodontic treatment in patients with ß-thalassemia major (BTM) and sickle cell disease (SCD). The study was conducted on 311 blood transfusion-dependent patients with BTM or SCD and 400 healthy individuals aged 10 to 16. The types of malocclusion were evaluated based on Angle's classification and Dewey's modification, and their oral habits were recorded using a questionnaire. The need for orthodontic treatment was assessed through the Dental Health Component of the Index of Orthodontic Treatment Need (IOTN), and the data were compared with normal participants. The Index of Orthodontic Treatment Need-Dental Health Component (IOTN-DHC) assessment showed that patients had a higher prevalence of objective need for treatment (IOTN grades 4 and 5) compared to healthy children. The prevalence of class II malocclusion was significantly higher in patients. Patients showed significantly less Angle's Class I malocclusion compared to normal participants. Oral habits were presented in 61%, 64.15% and 62.4% of normal participants, BTM and SCD patients, respectively. The higher prevalence of Angle's class II malocclusion and higher percentage of IOTN grade 4 and 5 among BTM and SCD patients reveal the importance of early orthodontic assessment and intervention in children with BMT and SDC.

Application of third-generation sequencing for genetic testing of thalassemia in Guizhou Province, Southwest China.

OBJECTIVES: To explore the application of third-generation sequencing (TGS) for genetic diagnosis and prenatal genetic screening of thalassemia genes. METHODS: Two groups of subjects were enrolled in this study. The first group included 176 subjects with positive hematological phenotypes for thalassemia. Thalassemia-associated genes were detected simultaneously in each sample using both the PacBio TGS platform based on single-molecule real-time (SMRT) technology and the conventional PCR-reverse dot blot (PCR-RDB). Sanger sequencing was used for validation when results were discordant between the two methods. The second group included 53 couples with at least one partner having a positive thalassemia hematological phenotype, and they were screened for homotypic thalassemia variants by TGS, and the risk of pregnancies with babies presenting with severe thalassemia, was assessed. RESULTS: Of the 176 subjects, 175 had concordant genotypes between the two methods, including 63 normal subjects and 112 α- and/or ß-thalassemia gene carriers, with a concordance rate of 99.43%. TGS detected a rare ß-thalassemia gene variant -50 (G > A) that was not detected by conventional PCR-RDB. TGS identified seven of the 53 couples as homotypic thalassemia gene carriers, five of whom were at risk of pregnancies with severe thalassemia. CONCLUSION: TGS could effectively detect common and rare thalassemia variants with high accuracy and efficiency. This approach would be suitable for prenatal thalassemia genetic screening in areas with high incidence of thalassemia.

Approach to the management of ß thalassemia major associated osteoporosis - A long-standing relationship revisited.

Adults with ß- thalassemia major (ß-TM) develop low BMD and fragility fractures at a higher incidence and at a younger age compared to the general population. The disease itself, including direct effects of anemia and iron overload toxicity on bone turnover, genetic susceptibility, thalassemia-related endocrinopathies and acquittance of suboptimal peak bone mass contribute to low bone mass and increased bone fragility frequently encountered among these patients. Current management of osteoporosis requires long-term treatment that can be provided by agents that reduce the risk of all osteoporotic fractures by modulating bone metabolism with different mechanisms of action. These include inhibitors of bone remodeling (e.g., bisphosphonates, denosumab) and stimulators of bone formation (e.g., PTHR1 agonists and sclerostin antibodies). Considering the unique characteristics of osteoporosis associated with ß-TM and the clinical importance of balancing the risk/benefit of treatment in the long-term, appropriate use of these therapeutic approaches is essential for patient care. In this review we outline current literature on the use of anti-osteoporotic drugs in ß-TM patients with osteoporosis focusing on data on the efficacy, safety, and duration of treatment. In addition, we propose a long-term management plan for ß-TM -associated osteoporosis aiming at the optimal patient care for this special population.

[Analysis of Gene Detection and Hematological Phenotype of Thalassemia].

OBJECTIVE: To investigate gene mutation types of thalassemia in the population of this area and the relationship between hematological phenotype and age in ß-thalassemia. METHODS: 1 351 suspected cases of thalassemia were detected in the First Affiliated Hospital of Chengdu Medical College from June 2017 to June 2021. PCR-reverse dot blot hybridization(PCR-RDB) technique was used to detect the common α and ß thalassemia gene types, then the data of MCV, MCH, MCHC and Hb of confirmed cases were collected. The heterozygotes of ß-thalassemia were divided into 0-18 year group, 19-50 year group and >50 year group according to age, and the differences of hematological phenotypes among different groups were compared. RESULTS: Among the detected 1 351 samples， 523(38.71%) cases were diagnosed as thalassemia, 13 genotypes were detected in 260 cases (19.25%) with α-thalassemia; and 12 genotypes were detected in 252 cases (18.65%) with ß-thalassemia; 9 genotypes were detected in 11 cases with αß thalassemia. It was found that MCV and MCH were increased significantly in 0-18 year group, 19-50 year group and >50 year group, MCHC was highest in 0-18 year group, and Hb was the lowest in the >50 year group, and the difference was statistically significant（P<0.05）. CONCLUSION: In this area, --SEA/αα was the major genotype of α-thalassemia, and CD41-42 /N and IVS-II-654/N were the major genotypes of ß-thalassemia. Morever, MCV and MCH were the lowest in the 0-18 year old group and the highest in the >50 years old group in heterozygotes of ß-thalassemia. The influence of age on hematological parameters in the primary screening of thalassemia provides a certain reference value in clinical diagnosis and treatment.

The population incidence of thalassemia gene variants in Baise, Guangxi, P. R. China, based on random samples.

OBJECTIVE: Thalassemia is a monogenic genetic disorder with a high prevalence in populations in the southern region of China. The thalassemia gene prevalence rate in the Baise population in China is high, and several rare gene variants have been detected in the population of this region during routine testing by our study group. To accurately reveal the thalassemia gene variants carried by the population in Baise, and to provide a basis for the formulation of thalassemia prevention and control policies in the region, we conducted a more comprehensive study in a randomly selected population. RESULTS: In all, 4,800 randomized individuals were recruited for testing from Baise, and the detection of hot spot thalassemia genetic variants were performed by Gap-PCR and PCR-RDB methods, combined with the relative quantification of homologous fragments and AS-PCR to expand the detection range. The prevalence of thalassemia variants in this population was 24.19%, among which 16.69% of individuals carried α-thalassemia gene variants alone, 5.62% carried ß-thalassemia gene variants alone, and 1.88% carried both variants. CONCLUSIONS: The use of positive primary screening combined with hot spot gene variant detection alone can result in a certain degree of missed detection. In the prevention and control of thalassemia in the region, testing institutions need to pay attention to the detection of rare thalassemia gene variants such as αααanti4.2, αααanti3.7, -α2.4, -α21.9, ß-50, ß-90, and ßIVS-II-5, to provide more accurate genetic counseling advice to subjects.

Combined Gap-Polymerase Chain Reaction and Targeted Next-Generation Sequencing Improve α- and ß-Thalassemia Carrier Screening in Pregnant Women in Vietnam.

Vietnam has a high thalassemia burden. We collected blood samples from 5880 pregnant Vietnamese women during prenatal health checks to assess thalassemia carrier frequency using combined gap-polymerase chain reaction (gap-PCR) and targeted next-generation sequencing (NGS). Thalassemia carriers were identified with prevalence of 13.13% (772), including 7.82% (460) carriers of α-thalassemia (α-thal), 5.31% (312) carriers of ß-thalassemia (ß-thal), and 0.63% (37) concurrent α-/ß-thal carriers. Deletional mutations (368) accounted for 80.0% of α-thal carriers, of which, --SEA (Southeast Asian) (n = 254; 55.0%) was most prevalent, followed by the -α3.7 (rightward) (n = 66; 14.0%) and -α4.2 (leftward) (n = 45; 9.8%) deletions. Hb Westmead (HBA2: c.369C>G) (n = 53) and Hb Constant Spring (Hb CS or HBA2: c.427T>C) (in 28) are the two most common nondeletional α-globin variants, accounting for 11.5 and 6.0% of α-thal carriers. We detected 11 different ß-thal genotypes. Hb E (HBB: c.79G>A) (in 211) accounted for 67.6% of ß-thal carriers. The most common ß-thal genotypes were associated with mutations at codon 17 (A>T) (HBB: c.52A>T), codons 41/42 (-TTCT) (HBB: c.126_129delCTTT), and codon 71/72 (+A) (HBB: c.217_218insA) (prevalence 0.70%, 0.68%, and 0.2%, respectively). Based on mutation frequencies calculated in this study, estimates of 5021 babies in Vietnam are affected with clinically severe thalassemia annually. Our data suggest a higher thalassemia carrier frequency in Vietnam than previously reported. We established that combining NGS with gap-PCR creates an effective large-scale thalassemia screening method that can detect a broad range of mutations.

[Molecular Epidemiological Characteristics and Differential Diagnosis of Common 뫧-Thalassemia/HPFH].

OBJECTIVE: To investigate the molecular epidemiological characteristics of common δß-thalassemia/hereditary persistence of fetal hemoglobin(HPFH) in the prepregnant population in Huadu, and to provide a laboratory basis for prevention and control of thalassemia. METHODS: Blood samples of childbearing age people in Huadu District of Guangzhou who participated in free thalassemia testing from January 2016 to July 2021 were collected for hematological parameters analysis and hemoglobin electrophoresis. Chinese Gγ+(Aγδß)0-thalassemia, SEA-HPFH and Taiwanese deletion ß-thalassemia were detected by Gap-PCR in the samples with higher HbF(≥5%). Primers were designed for the proximal HBG1 and HBG2 promoter, and the point mutations in the proximal promoter region were detected by Sanger sequencing. Hematology parameters data were statistically analyzed. RESULTS: Among 27 088 samples, Thirteen cases of Chinese Gγ+(Aγδß)0-thalassemia and thirty-three cases of SEA-HPFH were detected, which including 3 cases of Chinese Gγ+(Aγδß)0/ßN compounded with --SEA/αα and three cases of SEA-HPFH/ßN compounded with --SEA/αα. 6 carriers with Aγ-196 C>T were also detected; No Taiwanese thalassemia genetype was detected. The total detection rate of common δß-thalassemia/HPFH was 0.19% (52/27 088). There were significant differences in the levels of MCV, MCH, HbA2, and HbF among Chinese Gγ+(Aγδß)0-thalassemia, SEA-HPFH, Aγ-196 C>T (P<0.001). The hematological parameters of Aγ-196C>T combined with α0-thalassemia were similar to those of Chinese Gγ+(Aγδß)0-thalassemia carriers, and only HbA2 was significantly lower than that of the latter, which was helpful for clinical identification. CONCLUSION: δß-thalassemia/HPFH should be included in the scope of thalassemia prevention program in the prepregnant population in Huadu District, and hematological parameters can provide some basis for identifying different types of δß-thalassemia/HPFH.

The prevalence of sickling abnormality in Oman: A review of relevant publications

Sickle cell disease (SCD), caused by a mutation in the ß-globin gene HBB, is widely distributed in malaria endemic regions.  The prevalence of sickle cell trait and disease reaches up to 4.8-6% and 0.2% respectively, which is the highest among the Arab Gulf states.  Omani population represents a variability of HbS genotype combinations with other Hb genotypes modify the clinical severity of the disease. The most prevalent sickling abnormality in Oman is Hb S/S (SCA) followed by Hb S/ß-thalassemia. Omani children with SCD with high Hb F level had less severe disease. More than two-thirds of SCD cases were running a mild course of the disease due to the high prevalence of  a-thalassemia trait. The severity index has been correlated with the early age of presentation, the absence of  a-thalassemia trait and the lower level of HbF as well as to the existence of different ß-globin gene haplotypes.  S/ ß0 presented with the same clinical severity of S/S while those with S/ ß+ had some splenic function into adulthood and were more prone to splenic sequestration. The unique existence of HbS-Oman (a severe variant of sickle hemoglobinopathy) markedly increased the severity of the disease. Compound heterozygotes HbS-Oman resulted in very severe clinical manifestations with transfusion-dependency and hypersplenism early in life. This paper summarizes and reviews ßs gene haplotypes in patients with sickle cell anemia (SCA) in Oman. (www.actabiomedica.it).

Thalassemia in Malaysia.

Malaysia is a multi-ethnic nation, comprising of Malays and other indigenous groups (67.4%), Chinese (24.6%), Indians (7.3%) and others (0.7%). Thalassemia, which includes α- and ß-thalassemia (α- and ß-thal), is one of the most common genetic disease in Malaysia. Between 4.5 and 5.0% of the Malaysian population were reported to be carriers of this disease and 3.0-40.0% were Hb E (c.79G>A) carriers. In 2013, the Malaysian Thalassaemia Registry reported a total of 5712 registered thalassemia patients, of which 1847 had Hb E/ß-thal and 2329 had ß-thal major (ß-TM). Out of the total number of registered thalassemia patients, Malays comprise 62.0%, Chinese 13.0% and Kadazan-Dusun 13.0%. There were eight common deletions and mutations of the α-thal gene, including three double gene deletions, two single gene deletions, and three nondeletional mutations. The five types of ß-thal mutations generally found in the Malay ethnic group were codon 19 (A>G) (or Hb Malay (HBB: c.59A>G), IVS-I-1 (G>T) (HBB: c0.92+1G>T), IVS-I-5 (G>C) (HBB: 92+5 G>C), and polyadenylated signal (polyA) (AATAAA>AATAGA) (HBB: c.*112A>G). The structural variant, Hb E, accounted for 76.0% of the ß-thal mutations. Malaysia was positioned among the top countries in terms of having the best healthcare in the world in 2019 and this includes free access to three iron chelation agents for the treatment of thalassemia. The Malaysian National Programme for Thalassemia Prevention and Control was launched in 2004 and consisted of mass public education campaigns, public awareness and health education, Malaysian Thalassaemia Registry, population screening, laboratory diagnosis and comprehensive patient management.

Thalassemia in Viet Nam.

The population of Viet Nam, is 96.2 million, of which 13.8% are carriers of thalassemia genes. Thalassemia/hemoglobinopathies carriers exist at different frequencies in all 54 ethnic groups of the country. Gene carrier rate and globin gene mutation rate varies ethnically and topographically. The ethnic groups in the Northern Highland region have high rates of α0- and ß0-thalassemia (α0- and ß0-thal), while those in the Southern Middle region have high rates of α+-thalassemia (α+-thal) and Hb E (or codon 26) (HBB: c.79G>A). The lowest is found in La Hu (0.23%), while the highest is found in Raglai (88.6%). Thalassemia prevention and control programs were introduced using prenatal and neonatal diagnosis for the prevention of new thalassemic births. Most existing thalassemia patients are undergoing supportive treatment with regular blood transfusions and iron chelation. Curative treatment by hematopoietic stem cell transplantation is available but is limited to a minority of the patients.

Current Status of Thalassemia in Lao People's Democratic Republic.

Thalassemia is a major public health and economical burden in Lao People's Democratic Republic (Lao PDR). This study is aiming to elaborate the current situation of Thalassemia in Laos. α- and ß-thalassemia (α- and ß-thal) includes the common Hb S (HBB: c.20A>T) and hemoglobins (Hbs) such as Hb Constant Spring (Hb CS or HBA2: c.427T>C) and Hb E (HBB: c.79G>A) that are prevalent in the country. Overall, the prevalence of α-thal in Lao PDR is 26.8%. There was high prevalence of homozygous (12.8%) and heterozygous (39.7%) Hb E among migrant workers from Lao PDR who crossed the border to work in Thailand. Iron chelation, blood transfusion, prenatal screening and diagnosis, comprehensive treatment are still the major problems. Splenectomy is still performed. A national registry has still not been established. This is a national economic burden for the country. Thalassemia prevention and control strategy should be established and advocated by the government in order to reduce morbidity and premature mortality.

Thalassemia in Indonesia.

Indonesia is located along the 'Thalassemia Belt' and a hotspot for hemoglobinopathies. Around 3.0-10.0% of the population carry ß-thalassemia (ß-thal) and 2.6-11.0% of the population carry α-thalassemia (α-thal). It is estimated that around 2500 babies are born with ß-thal major (ß-TM) each year. At present, the cornerstone of treatment for ß-TM in Indonesia remains supportive, including blood transfusions and iron chelation therapy. Hemovigilance systems in some cities are poor and it increases the risk of transfusion-transmitted infections and transfusion reactions. The availability of iron chelators remains uncertain, even in some rural areas, iron chelators do not exist. The poor adherence to iron chelation therapy and maintaining pretransfusion hemoglobin (Hb) levels above 9.0 g/dL are still a major issue in Indonesia. The cost of blood transfusion and iron chelation are covered by national health insurance. In line with the rise of life expectancy, the financial burden of thalassemia in Indonesia is increasing sharply. Thus, optimizing preventive programs may be the most suitable option for the current thalassemia condition in Indonesia.

Thalassemia in Pakistan.

The estimated population of Pakistan is approximately 225,633,392 (225 million). The healthcare delivery system of Pakistan is complex because it includes healthcare subsystems operated by both the federal government and the provincial government. In Pakistan ß-thalassemia (ß-thal) trait frequency ranges between 5.0-7.0%, thus, there are more than 10 million carriers in the country; and every year, around 5000 children are diagnosed to carry ß-thal major (ß-TM) in Pakistan. No standard management protocols exist and blood transfusion remains the mainstay of management. Most of the population belong to the lower socioeconomic strata, family units are large and therefore cannot afford to pay for treatment and management of their thalassemic child. Currently in Pakistan, at the national level, not a single thalassemia prevention program is available to counter this disease. However, at the provincial level some initiatives have been taken, legislation has been approved for premarital screening in Sindh, Khyber Pakhtunkhwa (KPK) and Baluchistan, but implementation remains the issue.

Thalassemia Status in Cambodia.

The population of Cambodia (in 2019) was approximately 16 million with an annual growth rate of 1.4% in which the prevalence of hemoglobinopathies was estimated at about 40.0% (range 30.0-50.0%) to be carriers, and 2240 annual births for ß-thalassemia major (ß-TM). The overall prevalence of ß-thalassemia (ß-thal) and α-thalassemia (α-thal) were 40.9 and 39.6%, respectively. Currently, the specific epidemiological data regarding the abnormal gene frequency/mutations among different ethnic groups is unknown. In 2011, national guidelines for the Clinical Management of Patients with Thalassemia in Cambodia were developed and published by the Ministry of Health (MoH). Packed red cells (PRCs) are available at most referral hospitals (provincial hospitals). Oral iron chelators [deferiprone (DFP) and deferasirox (DFX)] are only available from a private pharmaceutical company. The future needs for Cambodia are to develop a national policy on the prevention or control of ß-thal and α-thal, and a national registry of patients with thalassemia, to determine the gene frequency of α- and ß-thal in different regions of the country, and to place the iron chelators on the list of essential medicines.

Thalassemia in Asia 2021 Overview of Thalassemia and Hemoglobinopathies in Bangladesh.

Bangladesh is a country with a population of 160 million with a gross national income per capita of US$1580.00. The major health problems in Bangladesh include acute respiratory infection, pneumonia, dengue fever, malaria and water-borne diseases. The health care system in Bangladesh is divided into primary secondary and tertiary levels, with each level having their own breakdown of available hospital beds and other treatment facilities. Thalassemia is a major health problem in Bangladesh. There are two types of thalassemia in Bangladesh: ß-thalassemia (ß-thal) and Hb E (HBB: c.79G>A)/ß-thal, with the prevalence rate of ß-thal trait being 4.1% and Hb E trait 6.1%. This study discusses spectrum types of thalassemia and hemoglobinopathies in Bangladesh and the types of carrier detection. The distribution of common mutations of thalassemia are also discussed and the distribution frequencies of genotypes and alleles of ß-thal and Hb E patients are also compared. Additionally, we also conducted a study of the spectrum of thalassemia using high performance liquid chromatography (HPLC) of the tribal populations and analyzed the findings in our discussion. The results of these studies show that the phenotypic and genotypic presentation in Bangladesh is highly diverse. To properly understand this, we have to conduct an epidemiological survey of the population. Furthermore, there also has to be improvement on the awareness of thalassemia among the population to properly equip themselves to survive this disease.

Thalassemia in Sri Lanka.

The island nation of Sri Lanka with 22 million people (in 2020) has an estimated 2000 patients with severe thalassemia. The majority have ß-thalassemia (ß-thal) major (ß-TM), and Hb E (HBB: c.79G>A)/ß-thal accounts for most of the remainder. Carrier rate for α+-thalassemia (α+-thal) trait is 9.9% and ß-thal trait is 2.5%, with very similar rates in the three major ethnic groups (Sinhalese, Tamils and Moors). The distribution of thalassemia type reveals a remarkable variation, even in this small island, mirroring historical distribution of malaria. Even though healthcare is provided free by the state including blood transfusions and chelation, the overall survival of patients of ß-TM is still not on a par with that of the Mediterranean countries. A national thalassemia prevention program was set up in 2007, but overall success of the exercise based essentially on dissuasion of marriages is not very promising.

Thalassemia in India.

Management and control of hemoglobinopathies are a challenge in India where 67.0% of people reside in rural regions. The GDP spent on health is one of the lowest (1.3%) resulting in high out-of-pocket expenses. The ß-thalassemias are prevalent with an estimated 7500-12000 new births each year. Hb S (HBB: c.20A>T) and Hb E (HBB: c.79G>A) are also common regionally. Over 80 ß-thalassemia (ß-thal) mutations have been characterized in Indians. The δ gene mutations are increasingly being described and their coinheritance in ß-thal carriers leads to a reduction in Hb A2 levels and a misdiagnosis of carriers. Around 15-20 centers offer prenatal diagnosis (PND) mainly in urban regions. The projected annual cost of care of ß-thal patients over a decade (2016-2026) will increase from INR30,000 (US$448) million to INR55,000 (US$820) million if all patients are adequately treated. Cost comparisons are difficult to make with other international studies as the standard of care, cost of medicines and other services vary in different countries. Several centers provide hematopoietic stem cell transplants (HSCTs) for thalassemias, however, only around 250 HSCTs are done annually. Although the cost is high, financial assistance is available for a few patients. There are disparities in the quality of care and to address this a National Policy has been proposed for the management and prevention of hemoglobinopathies that will embark on a comprehensive program, providing adequate care and augmenting the existing public health care services. It will also include training, genetic counseling and easier access to preventive options and a National Registry.

Clinical Severity of ß-Thalassemia Pediatric Patients in Myanmar.

ß-Thalassemia (ß-thal) is highly prevalent in Myanmar, but limited data are available on the molecular basis and the clinical manifestations in Myanmar patients. In this study, we investigated the clinical features and ß-globin gene abnormalities in 15 homozygous ß-thal and 60 Hb E (HBB: c.79G>A)/ß-thal pediatric patients who attended Yangon Children Hospital, the biggest thalassemia day care unit center in Myanmar. Eight different ß0-thal mutations were identified, with four accounting for 88.9% of alleles studied (excluding the Hb E variant). A genotype-phenotype correlation was found; all homozygous ß0-thalassemias had severe clinical courses, whereas the highly variable disease severity was demonstrated among Hb E/ß0-thal patients. Interactions of IVS-I-1 (G>T) (HBB: c0.92+1G>T) ß0-thal with Hb E are associated with milder clinical symptoms. The number of mildly affected Hb E/ß-thal patients was lower than expected, suggesting that there may be a considerable number of patients in the population who have either not been admitted to hospital or diagnosed with carrying the disease. Although the clinical severity in the Myanmar ß-thal patients seems to be similar to that in other populations, the levels of hemoglobin (Hb) appears to be very low. These findings indicate the need for the improvement of patient management and the development of prevention and control programs for ß-thal in Myanmar.

Genetic Background Studies of Eight Common Beta Thalassemia Mutations in Thailand Using ß-Globin Gene Haplotype and Phylogenetic Analysis.

Single nucleotide polymorphisms are informative for haplotype analysis associated with genetic background and clinical linkage studies of ß-thalassemia mutations. Hence, the aim of this study was to investigate five polymorphisms (codon 2 (C/T), IVS II-16 (C/G), IVS II-74 (G/T), IVS II-81 (C/T) and the Hinf I (T/A) polymorphism) on the ß-globin gene, related to eight common ß-thalassemia mutations in Thailand, including NT-28 (A > G), codon 17 (A > T), codon 19 (A > G), HbE (G > A), IVS I-1 (G > C), IVS I-5 (G > C), codon 41/42 (-TTCT) and IVS II-654 (C > T). The strongest LD (100%) between the ß-thalassemia mutation allele and all five SNPs was found in NT-28 (A > G), codon 17 (A > T) and codon 19 (A > G). In the haplotype analysis, we found three haplotypes (H1, H2 and H7) related to Hb E, whereas we only found two haplotypes related to codon 41/42 (-TTCT) (H1, H3) and IVS I-1 (G > C) (H3, H4). Of interest is the finding relating to a single haplotype in the remaining ß-thalassemia mutations. Furthermore, phylogenetic tree analysis revealed three clusters of these common ß-thalassemia mutations in the Thai population and enabled us to determine the origin of these mutations. Here, we present the results of our study, including four intragenic polymorphisms and the finding that the Hinf I polymorphism could be informative in genetic background analysis, population studies and for predicting the severity of ß-thalassemia in Thailand.