Detection of β-Thalassemia Mutations Using a Multiplex Amplification Refractory Mutation System Assay

We developed two sets of a multiplex amplification refractory mutation system (M-ARMS) assay to identify specific β-thalassemia (β-thal) mutations that are common in Thailand. The first one was for the detection of mutants with codon 17 (A>T), IV S-I-1 (G >T)), codons 41/42 (?TCT T) and codons 71/72 (+A), while the second one was for the ?87 (C>A), ?28 (A>G) and IVS-II-654 (C>T). Application of the proposed assay to 282 persons with β-thal trait revealed a positive result in 276 cases (97.8%). There were 258 cases (91.5%) positive for the set 1 M-ARMS assay and 18 cases (6.4%) were positive for set 2. Six cases (2.2%) were negative for both sets 1 and 2, and were further characterized by DNA sequencing. The mutations detected by the set 1 M-ARMS assay were 113 cases (40.1%) of codons 41/42, 95 (33.7%) of codon 17, 41 (14.5%) of IVS-I-1 and nine cases (3.2%) of codons 71/72, while by set 2 there were 12 cases (4.2%) of ?28, four cases(1.4%) of ?87 and two cases (0.7%) of IVS-II-654. Mutations undetectable by M-ARMS assay were two cases of codons 27/28 (+C), one case of codon 35 (C>A), one of codon 43 (G>T), one of ?31 (A>G) and one of IVS-I-5 (C>G).

The M-ARMS assay proved to be a valuable tool for the analysis of β-thal mutations. The method is robust, accurate, simple, speedy and cost-effective. The application of this assay will facilitate genetic counseling and prenatal diagnosis for severe thalassemia in high-risk pregnancies.     

Molecular Characterization of β-Thalassemia in North Jordan

We have studied the β-thalassemia mutations in 91 chromosomes of 43 patients with β-thalassemia major and five with Hb S-β-thalassemia, aged 6 months to 24 years. Many are blood transfusion-dependent and are being treated at the major hospital, the Princess Basma Hospital, in Irbid, Jordan. As many as 13 different mutations have been identified; three Mediterranean mutations [IVS-I-110 (G->A), IVS-II-1 (G->A), and IVS-II-745 (C->G)] were present in 54% of the chromosomes tested, while six other Mediterranean alleles were found in 24% of the chromosomes, for a total of 78% of Mediterranean origin. Sixteen chromosomes carried mutations which were observed in Arabian, Southeast Asian/Indian, and Iranian/Egyptian or Black populations; four β-thalassemia mutations remained unidentifed.     

Molecular Characterization of β-Thalassemia Mutations in Central Vietnam

The molecular basis of β-thalassemia (β-thal) mutations in North and in South Vietnam have been described during the past 15?years, whereas limited data were available concerning the central area of the country. In this study, we describe the molecular characterization and frequency of β-globin gene mutations in the Thua Thien Hue Province of Central Vietnam as the result of a first survey conducted in 22 transfusion-dependent patients, and four unrelated heterozygotes. Nine different known mutations were identified (seven of the β⁰ and two of the β⁺ type) in a total of 48 chromosomes. The most common was codon 26 (G>A) or Hb E (HBB: c.79?G>A) accounting for 29.2% of the total studied chromosomes, followed by codon 17 (A>T) (HBB: c.52?A>T) (25.0%), and codons 41/42 (–TTCT) (HBB: c.126_129delCTTT) (18.8%). Other mutations with appreciable frequencies (6.3–8.3%) were IVS-I-1 (G>T) (HBB: c.92+1?G>T), codon 26 (G>T) (HBB: c.79?G>T) and codons 71/72 (+A) (HBB: c.216_217insA). Relatively rarer (2.0%) were the promoter –28 (A>G) (HBB: c.78?A>G) mutation, the codon 95 (+A) (HBB: c.287_288insA), which is reported only in the Vietnamese, and the codons 14/15 (+G) (HBB: c.45_46insG) mutation, thus far observed only in Thailand. Results are relevant for implementing appropriate measures for β-thal prevention and control in the region as well as in the whole country.     

Characterization of β-Thalassemia Mutations Among the Japanese

Characterization of β-thalassemia mutations were attempted for 29 Japanese families clinically diagnosed as having β-thalassemia. Following the identification of a mutation by cloning and sequencing, all families were screened for this particular mutation, using biotinylated allele-specific oligonucleotide probes. Seven different mutations were detected in 17 families: Six families had the frameshift mutation at codons 41/42, resulting from a 4 nucleotide deletion (TTCTTT+- - - - TT); four had the deletion at codons 127/128 (CA66CT+CCT); and three had the TATAbox mutation at nucleotide -31 (A →6). Four additional families had mutations at codon 24 (GGT →GGA), codon 26 (GAG→AAG), IVS-11-654 (C →T) and codon 110 (GTG → CCG), respectively. The newly discovered deletion mutation at codons 127/128, and mutations at nucleotide -31, and at codon 110 are peculiar to Japanese, and have not been found in any other ethnic group. The haplotypes of the β-globin gene cluster were also determined. Some of the haplotypes and β-thalassemia mutations are identical to those reported in the Chinese population. However, it is noteworthy that nearly half of the β-thalassemia mutations were unique to Japanese.     

β-Thalassemia in China: a Systematic Molecular Characterization of β-Thalassemia Mutations

In order to initiate a program of prenatal diagnosis for the prevention of β-thalassemia in China, we have begun systematic studies of the β-thal assemia mutations among the Chinese. DNA polymorphisms in the β-globin gene cluster were examined in 46 β-thalassemia chromosomes. Six different haplotypes were observed. One β-thalassemia gene associated with a new haplotype was cloned and sequenced. The mutation was a single base substitution (A→G) at position -29 within the highly conserved proximal promoter element (the “TATA” box). This mutation was not observed previously in the Chinese. The β-thalassemia genes were further screened with oligonucleotide probes specific for all known mutations in the Chinese. Five mutations were identified and accounted for 35 β-thalassemia alleles.     

Molecular Update of β-Thalassemia Mutations in the Syrian Population: Identification of Rare β-Thalassemia Mutations

β-Thalassemia (β-thal) is an autosomal recessive disorder characterized by variable degrees of anemia, bone marrow hyperplasia, splenomegaly, and complications related to the severity of the anemic state. The β-thalassemias result from mutations in and around the β-globin gene (HBB) located as a cluster on the short arm of chromosome 11. In Syria, β-thal is highly prevalent. The main aim of this study was to identify the frequency of HBB mutations in 189 Syrian β-thal patients and carriers of β-thal. Out of the 189 patients and carriers recruited in this study, 181 patients had at least one HBB mutation and eight patients did not show any mutation. The 10 most frequent ones constituted 77.5% of all HBB mutations. These mutations in order of frequency were: IVS-I-110 (G?>?A) (17.0%), IVS-I-1 (G?>?A) (14.7%), codon 39 (C?>?T) (14.4%), IVS-II-1 (G?>?A) (9.8%), codon 8 (–AA) (6.2%), IVS-I-6 (T?>?C) (5.2%), IVS-I-5 (G?>?C) (4.9%), codon 5 (–C) (3.2%), IVS-I-5 (G?>?A) (3.2%) and codon 37 (G?>?A) (2.2%). Another 21 mutations were less frequent or sporadic. These results provide important tools for adapting a prenatal molecular diagnostic test for the Syrian population.     

Molecular Updating of β-Thalassemia Mutations in the Upper Egyptian Population

We have updated the dataset of the molecular spectrum of the β-thalassemia (β-thal) in Upper Egypt. Buccal swabs were analyzed from 94 unrelated patients with β-thal major (β-TM) using reverse dot-blot and multiplex amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). The most frequent mutation was IVS-I-110 (G>A) (57%). The IVS-I-110, IVS-I-6 (T>C) and IVS-I-1 (G>A) mutations accounted for 87% of the β-thal anomalies. The codon 39 (C>T) and frameshift codon (FSC) 6 (–A) (GAG>–GG) mutations were only detected in Al-Minya and Qina, respectively. We did not observe the IVS-II-745 (C>G) or –101 (C>T) mutations. Forty-three percent of Upper Egyptians were homozygotes. Our efforts were an important step to complete the mutation map of β-thal in Egypt restricted to Cairo and the Nile Delta regions. This study will help to develop preventative programs for Upper Egyptians. It addressed the genetic drift of the β-thal gene mutations in Africa, Asia, and Europe.     

Molecular Characterization of β-Thalassemia in the Dohuk Region of Iraq

β-Thalassemia (thal) is an important health problem in the Dohuk region of northern Iraq because of its high carrier rate and the frequency of consanguineous marriages. Thus, the need to establish an effective preventative program is paramount. As part of this effort, we initiated this study to determine the molecular basis of this disorder in the region. For the latter purpose, either parent of 104 registered β-thal major/intermedia patients had their full blood counts, hemoglobin (Hb) electrophoresis, Hb A₂ and Hb F quantitation performed. Their DNA was extracted, amplified and reverse hybridized to specific oligonucleotide probes to detect 20 β-thal mutations. The testing detected 12 β-thalassemic mutations. The eight most frequent were: IVS-II-1 (G→A), codon 44 (–C), codon 5 (–CT), IVS-I-1 (G→A), codon 39 (C→T), IVS-I-6 (T→C), codons 8/9 (+G) and IVS-I-5 (G→C). These mutations accounted for 81.7% of the thalassemic defects in the studied individuals. The less frequent mutations were: codon 8 (–AA), IVS-I-110 (G→A), codon 30 (G→C) and codon 22 (?7 bp), and the β-thalassemic defects remained uncharacterized in 11.5% of cases. This is the first study of β-thal mutations from Iraq, and shows a frequency of thalassemic defects different from those reported in surrounding countries. It provides a foundation for prenatal genetic testing that will be part of a thalassemia prevention program in the Dohuk region.     

Analysis of Common β-Thalassemia Mutations in North Vietnam

Available and flexible choice of methods for screening and detecting β-thalassemia (β-thal) can promote control of thalassemia in developing countries. In this study, two methods, the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and reverse dot-blot hybridization assays were developed to detect common β-thal mutations in 244 thalassemia patients and 152 healthy people in North Vietnam. The most common mutation was codon 26 (G>A), also known as Hb E (HBB: c.79G>A), accounting for 26.4% of the total studied chromosomes, followed by codons 41/42 (–TCTT) (HBB: c.126_129delCTTT) and codon 17 (A>T) (HBB: c.c.52A>T), accounting for 19.4 and 16.4%, respectively. In addition, codon 95 (+A) (HBB: c.c.287_288insA) that is known as the Vietnamese mutation, accounted for 0.6%. Moreover, the heterozygous state of the four mutations was also found in healthy people, of which Hb E was again the most common mutation with a frequency 3.0%. The results of this study provide available methods and indicative data for preventive and control strategies concerning the genetic diagnosis of thalassemia.     

Molecular Spectrum of β-Thalassemia Mutations in Northwestern Iran

β-Thalassemia (β-thal) is a hereditary autosomal disorder with decreased or absent β-globin chain synthesis. This study was designed to identify the common and rare β-thal mutations in the Azerbaijan provinces, Northwestern Iran, and to set up a prenatal diagnostic laboratory. One hundred unrelated patients with known β-thal major and intermedia, registered with the thalassemia clinics in the provincial capitals of Tabriz and Ardebil, were included. Mutations were studied in 200 chromosomes, by polymerase chain reaction-amplification refractory mutation system (PCR-ARMS) and direct sequencing methods. We found 17 β-thal mutations in this region of Iran. The results showed that IVS-II-1 (G→A) was the most frequent mutation, comprising 21% of all mutations. Other common mutations were IVS-I-110 (G→A) 18%, frameshift codons (FSC) 8/9 (+G) 14.5%, FSC 8 (?AA) 8% and IVS-I-1 (G→A) 7.5%. This is the first comprehensive study in this region and could be useful for developing a β-thal molecular screening in Azerbaijan-Iran     

Molecular Characterization of β-Thalassemia in the Czech and Slovak Populations: Mediterranean,Asian and Unique Mutations

β-Thalassemia (β-thal) is considered rare in Central Europe. As in other malaria-free regions, the presence of β-thal in Central Europe reflects historical and recent immigration, and demographic changes that have influenced the genetic variability of the current populations living in this area. This study assesses the frequency and spectrum of mutations on the β-globin gene in Czech and Slovak subjects with clinical symptoms of thalassemia. The results of the initial part of this research were published more than two decades ago; the aim of this study was to update these original reports. During the period from 2002 to 2015, 400 cases from Czech and Slovak hematological centers were analyzed. Twenty-nine β-thal mutations, identified in 356 heterozygotes from 218 unrelated families, involve five unique mutations including a recently described insertion of a transposable L1 element into the β-globin gene. One mutation described here is reported for the first time. Most of the mutations were of Mediterranean origin and accounted for 82.0% of cases. All but one case studied were heterozygous carriers, manifesting β-thal minor, with rare exceptions represented by the rare (β⁰) codons 46/47 (+G) (HBB: c.142_142dupG) mutation associated with an α-globin gene quadruplication and by dominantly inherited β-thal with a more severe phenotype. One double heterozygous β-thal patient was a recent immigrant from Moldavia. The list of δβ-thal alleles (26 carriers, 16 families) contains Hb Lepore and two types of δβ⁰-thal deletions. In the past, genetic drift and migration as well as recent immigrations were responsible for the introduction of Mediterranean alleles, while several mutations described in single families were of local origin.     

Molecular Basis of β-Thalassemia in the Western Province of Saudi Arabia: Identification of Rare β-Thalassemia Mutations

This study aimed at the identification of the spectrum of mutations in patients with β-thalassemia (β-thal) in the western province of Saudi Arabia. Screening for the mutations was done using the polymerase chain reaction-amplification refractory mutation system (PCR-ARMS) technique to test for 12 mutations, and direct automated DNA sequencing for the unknown samples. The study included 172 patients; of these 15 patients had sickle cell anemia and one Hb S [β6(A3)Glu→Val, GAG>GTG]/β-thal. A total of 23 mutations were identified to cause the disease in the western area. Seven common mutations were responsible for the β-thal alleles in 78% of patients and could be detected by the ARMS technique: IVS-II-1 (G>A), IVS-I-110 (G>A), IVS-I-5 (G>C), codon 39 (C>T), codon 26 (G>A) [Hb E or β26(B8)Glu→Lys, GAG>AAG], frameshift codons (FSC) 8/9 (+G), and IVS-I-1 (G>A). DNA sequencing of uncharacterized alleles detected eight less common mutations: FSC 41/42 (–TCTT), IVS-I 25 bp deletion, codon 37 (G>A), FSC 44 (–C), Cap site +1 (A>C), IVS-I-6 (T>C), FSC 5 (–CT) and IVS-I-1 (G>T), and eight rare mutations: ?87 (C>G), initiation codon ?1 (T>G), codon 15 (G>A), FSC 16 (–C), FSC 20/21 (+G), codon 27 (G>A), IVS-I-130 (G>C) and IVS-II-837 (A>C). Four alleles were normal by DNA sequencing. Genetic heterogeneity was observed in this study, 10 mutations were of Asian or Asian/Indian origin, two were Kurdish, one Chinese, one Turkish, one Saudi, and the remainder were of Mediterranean origin. The presence of a large population of immigrants in the western province is responsible for the great heterogeneity at the molecular level, and for the difference observed in the frequencies of mutations from those reported in the eastern province of Saudi Arabia. Screening for β-thal mutations using PCR-ARMS for the seven most frequent mutations in the Saudi population followed by DNA sequencing of the unknown alleles could be useful for the implementation of a strategy for carrier detection and preimplantation genetic diagnosis in high risk families.     

Molecular Characterization of β-Thalassemia in Nineveh Province Illustrates the Relative Heterogeneity of Mutation Distributions in Northern Iraq

Beta thalassemia is an important health problem in Nineveh province, a large province in Northwestern Iraq. No previous study of significance had focused on the spectrum of β-thalassemia mutations in this part of the country. A total of 94 unrelated β-thalassemia minor subjects from the latter province were recruited. Their carrier status was confirmed by full blood count, Hb A2 and F estimation. Thereafter their DNA was subjected to multiplex polymerase chain reaction and reverse hybridization to detect 20 β-thalassemia mutations. A total of eleven different β-thalassemia mutations were documented. The most frequent mutation was IVS-I-110 (G>A) documented in 34 %, followed by IVS-I-6 (T>C) in 9.6 %, IVS-I-5(G>C) in 8.5 %, codon 39 (C>T) and codon 44 (−C) in 7.4 % each, while IVS-I-1(G>A) and IVS-II-1(G>A) were encountered in 6.4 % each. Other mutations were less frequent including codon 8 (−AA), IVS-I-130 (G>C), codon 5 (−CT) and IVS-II-745(C>G). The current study revealed notable differences in the relative frequencies of several β-thalassemia mutations in Nineveh province as compared to other parts of Northern Iraq. Such an observation may be reflective of different ethnic backgrounds and varying historical population interactions. It is believed that these findings complement those of earlier studies on β-thalassemia mutations from the country, and are quite essential in the setting of a proposed national preventive program.     

The Molecular Analysis of β-Thalassemia Mutations in Lorestan Province,Iran

β-Thalassemia (thal) is one of the most common genetic disorders in Iran and other countries. Getting information on the distribution of mutations in different ethnic groups of Iran is of fundamental importance for the purpose of health planning and prenatal diagnosis programs. One hundred and thirty chromosomes from 65 unrelated homozygous β-thal patients were investigated for β‐globin gene mutations by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). The most common mutations of the Mediterranean region were examined in this study. Our results showed that the frameshift codons (FSC) 36/37 (–T) mutation, with a frequency of 33.8%, is the most common mutation in Lorestan Province. The other most frequent mutations were of the Mediterranean type and consisted of IVS-II-1 (G?→A), IVS-I-110 (G?→A), FSC 8/9 (+G) and IVS-I-5 (G?→C) with frequencies of 27.7, 11.5, 10.8 and 4.5%, respectively. The less frequent alleles, IVS-II-745 (C?→G), FSC 5 (–CT), IVS-I (25 bp deletion) and FSC 44 (–C) accounted for only 3.9% of the mutations. The unknown alleles comprised 7.7% of the mutations. These data showed that the spectrum of mutations found in Lorestan Province was different from those reported from other thalassemic regions of Iran and also of some neighboring countries.     

Population-Based Genetic Study of β-Thalassemia Mutations in Mardan Division,Khyber Pakhtunkhwa Province,Pakistan

β-Thalassemia (β-thal) is the most prevalent hereditary blood disorder in Pakistan with a carrier rate of 5.0–8.0%. The homozygous affected children require frequent blood transfusions for their survival. This autosomal recessive disease can only be prevented through awareness programs, carrier screening, mutation detection, genetic counseling and prenatal diagnosis (PND). The present study aimed to determine the prevalence of various mutations causing β-thal and also to detect carriers of these mutations in families living in the Mardan Division, Khyber Pakhtunkhwa (KP) Province, Pakistan. The study was conducted at the Department of Biochemistry, Abdul Wali Khan University Mardan, Pakistan. Blood samples of β-thalassemic families were collected from various transfusion centers in Mardan Division. Using the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) technique, all samples were analyzed for the six most common mutations causing β-thal in this area. Six different mutant primers for the detection of different mutations were used. The most common mutations detected in thalassemic patients were frameshift codons (FSC) 8/9 (+G) (HBB: c.27_28insG), codons 41/42 (–TTCT) (HBB: c.126_129delCTTT), and IVS-I-5 (G>C) (HBB: c.92+5G>C). The predominant mutation for carrying the mutant genes for β-thal were FSC 8/9, IVS-I-5, codons 41/42, IVS-I-1. It was also found that 66.7% of marriages were consanguineous. The FSC 8/9 mutation was found to be the most common β-thal mutation with a frequency of 44.4%. This research project provides a strong incentive for the establishment of large scale mutation detection and PND services in the Mardan Division.     

Hematological and Molecular Analysis of Novel and Rare β-Thalassemia Mutations in the Indian Population

A variety of mutations causing β-thalassemia (β-thal) have been seen in the Indian subcontinent. We report eight families in whom two novel mutations [codon 16 (C>T), IVS-II-613 (C>T)] and three rare mutations [codons 22/23/24 (?7 bp) (?AAGTTGG), ?87 (C>A), codon 15 (?T)] were encountered among 375 β-thal heterozygotes. They were referred to us for molecular characterization or prenatal diagnosis during a period of 2 years. Haplotyping was also done for linkage analysis.     

Distribution of β-Thalassemia Mutations in the Northern Provinces of Iran

β-Thalassemia (thal) is one of the most common autosomal recessive disorders in Iran. There are more than two million carriers of β-thal and over 15,000 people affected with β-thal major who live in Iran. Prevalent mutations were identified by examining genomic DNAs isolated from 392 blood samples of β-thal carriers from three northern provinces of Iran. Furthermore, 172 pregnant women were analyzed from the 196 couples who requested pregnant diagnosis for β-thal. Allele identification was carried out using routine reverse dot-blot, amplification refractory mutation system (ARMS), and genomic sequencing. The most common mutation, IVS-II-1 (G→A), is followed, in order of frequency, by codon 30 (G→C), frameshift codons (FSC) 8,9 (+G), FSC 22/23/24 (?AAGTTGG), IVS-I-110 (G→A), IVS-I-5 (G→C), IVS-II-745 (C→G), IVS-I-2 (T→C), FSC 8 (?AA), IVS-I,3′-end (?25 bp), IVS-I-1 (G→A), FSC 36/37 (?T), IVS-I-6 (T→C), FSC 5 (?CT), ?28 (A→C), codon 37 (G→A), IVS-II-2,3 (+11/?2), ?30 (T→A), and ?88 (C→A). We have also revealed the existence of five new mutations from northern Iran, one of which (codon 37) is the first reported for Iran. Furthermore, the rate of unknown mutations is significantly reduced in our study (about 6%). These results could help with establishing a center for prenatal diagnosis, prevention, and control of thalassemia in the northern provinces of Iran.     

Molecular Characterization and Phenotypical Study of β-Thalassemia in Tucumán,Argentina

The main hereditary hemoglobin (Hb) disorder in Argentina is β-thalassemia (β-thal). Molecular studies performed in the center of the country exhibited a marked prevalence of the codon 39 (C?>?T) and IVS-I-110 (G?>?A) mutations. The northwest region of Argentina has a different demographic history characterized by an important Spanish influx. Seventy-one β-thal carriers attending the Instituto de Bioquímica Aplicada, Tucumán, Argentina, were investigated for β-globin gene mutations by real-time polymerase chain reaction (RT-PCR). To examine the genotype-phenotype relationship, mean corpuscular volume (MCV), mean corpuscular Hb (MCH) and Hb A₂ were measured. In order to recognize β-thal, Mentzer Index, Shine &; Lal and Red Cell Distribution Width Index (RDWI), were calculated. The ethnic background of subjects revealed that 82.0% of the population was of Italian, Spanish and Arab origin. Seven mutations were detected: codon 39 (45.0%), IVS-I-1 (G?>?A) (22.5%), IVS-I-110 (16.3%), IVS-II-1 (G?>?A) (4.1%), IVS-I-1 (G?>?T) (2.0%), IVS-I-6 (T?>?C) (2.0%) and IVS-II-745 (G?>?C) (2.0%). In three families (6.1%), β-thal mutations were not determined. These results differed from other Argentinian studies because at present codon 39 and IVS-I-1 are the most prevalent; MCV, MCH and Hb A₂ did not correlate with the type of mutation (β⁰/β⁺). Values of MCV (67.0?fL) and Hb A₂ (4.85%) were unable to discriminate between them. Significant differences (p?相似文献   

Molecular Prenatal Diagnosis of α-Thalassemia Using Real-Time and Multiplex Polymerase Chain Reaction Methods

Molecular analysis of two fetuses at high risk of α-thalassemia (α-thal), and their family members, was performed using real-time polymerase chain reaction (PCR) with SYBR Green 1 (SYBR-PCR) dye combined with dissociation curve analysis and multiplex PCR (m-PCR) and DNA sequencing techniques. The genotype of the fetus from one family was – –^SEA/– –^SEA (Southeast Asian deletion), which produces hydrops fetalis syndrome. The genotype of the parents was – –^SEA/αα. A boy with Hb H disease and his sibling fetus from the other family had the genotype – –^SEA/α^CSα [the Hb Constant Spring (CS) mutation: α142, Term→Gln (TAA>CAA in α2)] and αα/αα (normal), respectively. The diagnosis, based on SYBR-PCR combined with dissociation curve analysis, was in agreement with the results from the m-PCR method. This indicates that these are alternative and reliable assays for the molecular diagnosis of deletional α-thal.     

Molecular Basis of β-Thalassemia in the Population of the Aegean Region of Turkey: Identification of A Novel Deletion Mutation

Abstract

β-Thalassemia (β-thal) is the most common monogenic disorder in Turkey. The aim of this study was to investigate the spectrum of β-thal mutations in the Aegean region of Turkey. The data was derived from 1171 unrelated β-thal subjects, detected in a regional reference hospital between November 2004 and December 2013. Screening for the 22 common mutations was performed using the polymerase chain reaction (PCR)-reverse dot-blot method, and direct automated DNA sequencing for the unknown samples. Thirty-one different β-thal alleles were identified. Seven mutations, namely IVS-I-110 (G?>?A) (41.7%), IVS-I-1 (G?>?A) (8.9%), IVS-II-745 (C?>?G) (8.6%), codon 8 (–AA) (7.7%), IVS-II-1 (G?>?A) (7.2%), IVS-I-6 (T?>?C) (6.6%), codon 39 (C?>?T) (4.6%) accounted for 85.3% of the mutated alleles. Frequencies of the remaining 24 β-thal mutations were less than 2.2%; these included one novel mutation [HBB: c.206_212del (p.Leu69Profs*19)], and four others [–56 (G?>?C), codon 16 (–C), IVS-I (–3) (C?>?T) (codon 29), codon 76 (–C)] found in Turkey for the first time. The results will help to prevent severe β-thal through genetic counseling and prenatal diagnosis (PND) in the Aegean region of Turkey.