Compound Heterozygote of Hb S (HBB: c.20A>T)/Hb Westdale (HBB: c.380_396delTGCAGGCTGCCTATCAG): Report of Four Cases from Odisha State,India

We report four cases of compound heterozygotes for Hb S (HBB: c.20A>T) and a rare β⁰-thalassemia (β⁰-thal) mutation, Hb Westdale (HBB: c.380_396delTGCAGGCTGCCTATCAG), characterized by a 17?bp deletion between codons 126 to 131 in exon 3 of the β-globin gene of human hemoglobin (Hb) confirmed by direct β-globin gene sequencing. All four cases were from four unrelated families belonging to the Agharia caste, an endogamous ethnic community of the Sundargarh and Jharsuguda districts of Odisha State, India. Detailed observations indicated that all four cases of Hb S/Hb Westdale were clinically severe. On family screening, six family members were found to be heterozygous for Hb Westdale and were asymptomatic. Deletional α-thalassemia (α-thal) and XmnI polymorphism were studied for all the Hb Westdale cases. The Hb S/Hb Westdale cases had an early median age at onset of symptoms and presentation, more requirement of blood transfusions, splenomegaly and hepatomegaly and were found to be clinically more severe when compared with the Hb S-β-thal with IVS-I-5 (G>C) (HBB: c.92?+?5G>C) cases. Overall, the findings indicate that this rare and hitherto unreported compound heterozygosity of Hb S/Hb Westdale is a clinically significant hemoglobinopathy and its finding in a large endogamous community of Odisha State, India will have important implication in the epidemiology and understanding of the clinical spectrum of sickle cell disease in Indian context and prenatal diagnosis.     

Prenatal Molecular Diagnosis of β-Thalassemia and Sickle Cell Anemia in the Syrian Population

Our objective was to evaluate the prenatal diagnosis (PND) of β-thalassemia (β-thal) and sickle cell anemia in Syria. Mutations detected from blood of at-risk couples and 55 amniotic fluid samples collected at the second trimester of pregnancy (14–22 weeks’ gestation) were characterized. Molecular screening and direct DNA sequencing of the HBB gene was carried out. DNA analyses showed 14 affected fetuses (25.45%), 32 (58.18%) carriers and eight (14.54%) normal fetuses. It appears that 20.0% of individuals carried the sickle cell anemia mutation and 80.0% carried the β-thal mutation. Thirteen different known mutations were detected in the fetuses. The most common mutations were: IVS-II-1 (G?>?A), codon 39 (C?>?T)], IVS-I-110 (G?>?A), IVS-I-1 (G?>?A) and IVS-I-5 (G?>?C). The Hb S [β6(A3)Glu?→?Val; HBB: c.20A?>?T] mutation was the only abnormal hemoglobin (Hb) that was found. The results point to a successful future for PND of β-thal and sickle cell anemia in Syria, using a rapid and accurate molecular method. We hope that this method will be used as a common application approach to decrease the incidence of β-thal major (β-TM).     

Genetic Background of β-Thalassemia in Northeast Algeria with Assessment of the Thalassemia Severity Score and Description of a new β0-Thalassemia Frameshift Mutation (HBB: c.374dup; p.Pro126Thrfs*15)

Abstract

β-Thalassemia (β-thal) is a genetic disorder representing a major health problem in Algeria. Our first objective was to determine the allelic frequencies and molecular spectrum of β-thal mutations in patients with major hemoglobinopathies [β-thal major (β-TM) and sickle cell disease] in three provinces of northeast Algeria. Our second objective was to assess if the clinical management of β-TM patients depended on their region of origin. Our last objective was to assess a population originating from Maghreb, the reliability of the thalassemia severity score (TSS) for patients with homozygous β-thal. Sanger HBB gene sequencing was performed on 59 patients with sickle cell disease and 60 with β-TM. For the latter patients, the genetic modifiers of the TSS were genotyped: α-thalassemia (α-thal) deletions and four Hb F-inducing polymorphisms (XmnI, rs1427407 and rs10189857 for BCL11A and rs9399137 for HMIP). Eleven different β-thal mutations were found but two of them (HBB: c.118C>T and HBB: c.93-21G>A) accounted for about 70.0% of the β-thal alleles. A relatively high proportion of Hb S (HBB: c.20A>T)/β-thal genotypes (27.0%) was found in our sickle cell disease cohort where a new frameshift β⁰-thal mutation (HBB: c.374dup; p.Pro126Thrfs*15) was identified. No difference was found in the three provinces. Of the 60 β-TM patients, those with a high or very high TSS were significantly younger at the age of first transfusion, thus assessing the reliability of this scoring system in a Maghrebin cohort. Trends for a lower age of splenectomy and high ferritin levels were also detected for the higher TSS categories.     

A Novel Pathogenic β-Thalassemia Mutation Identified at Codon 8 (HBB: c.27delG) in a Bangladeshi Family Acquired De Novo

Abstract

In Bangladesh, the practice of β-thalassemia (β-thal) carrier screening and prenatal diagnosis (PND) by β-globin gene sequencing has been initiated to prevent the birth of affected children. The study aimed to describe a novel de novo mutation of the β-globin gene and its clinical implication. Out of 100 Bangladeshi β-thal carrier families, one patient with hematological and clinical features associated with β-thal and her parents were included. Molecular characterizations of β-globin gene mutations were performed by direct sequencing. A novel nucleotide deletion mutation at codon 8 in the first exon of the β-globin gene (HBB: c.27delG) was found in a 1-year-old child of the studied family in a heterozygous state along with common Hb E (HBB: c.79G>A). The mutation caused a frameshift to a new stop codon at codon 18 resulting in a β⁰-thal phenotype. The proband exhibited a β-thal intermedia (β-TI)-like genotype, however, showed β-thal major (β-TM)-like complications and was transfusion-dependent. Her mother had a profile consistent with the Hb E trait, while the father had normal hematological indices. Mutation analyses revealed the mother to be heterozygous for Hb E, while the father had a normal genotype. The novel mutation was assumed to be inherited de novo by the paternity test. The study documented a novel pathogenic mutation in the β-globin gene in a Bangladeshi family by β-globin gene sequencing.     

Rare β-Globin Gene Mutations in Pakistan

The aim of this study was to analyze the rare β-thalassemia (β-thal) mutations in the Pakistani population. A total of 8716 unrelated Pakistani individuals having children with transfusion-dependent thalassemia were investigated by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) for the previously reported common and rare β-thal mutations. Genomic sequencing of the β-globin gene and its immediate 5' and 3' flanking regions was done where no known mutation was found. Out of the 8716 individuals studied, 88 (1.0%) were not characterized by ARMS-PCR. Genomic sequencing revealed that 67 (0.82%) individuals had 19 different β-thal mutations including one novel mutation (HBB: c.136delT). The remaining 21 (0.26%) individuals did not show any mutation on the β-globin gene and its immediate flanking regions. The characterized alleles included seven (0.09%) in the 5' untranslated region (5'UTR), 29 (0.35%) in the coding regions, and 31 (0.38%) in the splice junction regions. HBB: c.92+1G>A and HBB: c.113G>A were the most frequently seen rare mutations. The spectrum of β-thal mutations in the Pakistani population is very diverse. In addition to the already reported mutations, another 19 different types of mutations were found. Interestingly, 21 individuals who had children with transfusion-dependent thalassemia and one known β-thal mutation, did not show any mutation on the β-globin gene. HBB: c.92+1G>A and HBB: c.113G>A are the most frequently seen rare mutations in Pakistan.     

Molecular Characterization of β-Thalassemia Mutations Via the Amplification Refractory Mutation System-Polymerase Chain Reaction Method at the North Waziristan Agency,Pakistan

β-Thalassemia (β-thal) is a monogenic disease characterized by mutations on the HBB gene, affecting the production of globin that results in hypochromic and microcytic anemia. The aim of this study was to determine the prevalence of six common β-thal mutations, and their frequency and inheritance pattern in affected populations of North Waziristan Agency, Pakistan. In this study, 130 blood samples from 37 unrelated β-thalassemic families having a minimum of one transfusion-dependent child with β-thal major (β-TM), were retrieved either from the Thalassaemia Centre for Women and Children Hospital Bannu or their home towns situated in Noth Waziristan Agency. All samples were analyzed by the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) using six allele-specific primers for the presence of the six β-thal mutations common in the Pakistani population. Of the six common mutations, our study demonstrated five HBB mutations comprising HBB: c.27_28insG, HBB: c.92+5G>C, HBB: c.126_129delCTTT, HBB: c.92+1G>T and HBB: c.17_18delCT from the families studied, while mutation HBB: c.47G>A [codon 15 (G>A)] was not detected in any of the studied families. Furthermore, the HBB: c.27_28insG and HBB: c.92+5G>C were noted to be the most common with frequencies of 42.85 and 31.42%, respectively. The findings of the present study may be useful in launching carrier screening and prenatal diagnosis (PND) programs by screening analyzed and other unanalyzed affected families for the possible presence of common mutations through the ARMS-PCR technique that will help to control the disease.     

The Spectrum of β-Thalassemia Mutations in Hamadan Province,West Iran

β-Thalassemia (β-thal) is one of the most common hemoglobinopathies worldwide and is caused by mutations on the β-globin (HBB) gene. The aim of the present study was to determine the mutation spectrum of the β-globin gene in β-thal carriers who were originally from Hamadan Province, Western Iran. Two hundred and eighty-two β-thal carriers participated in the study. Amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and direct sequencing were used for detection of different mutations. A total of 25 different mutations, including 21 β-thal mutations and four other hemoglobin (Hb) variants, in 280 β-thal carriers (99.3%) were detected in the present study. Three types of mutations including IVS-II-1 (G>A) (HBB: c.315+1G>A) (26.24%), codons 8/9 (+G) (HBB: c.27_28insG) (14.54%) and codons 36/37 (–T) (HBB: c.112delT) (12.76%) accounted for more than 50.0% of the identified mutations. Moreover, IVS-I-110 (G>A) (HBB: c.93-21G>A), codon 44 (–C) (HBB: c.135delC) and IVS-I (25?bp deletion) (HBB: c.93-21_del), had frequencies of 7.09, 7.09 and 5.67%, respectively. Allele frequencies of the remaining 19 mutations were less than 5.0%. This study is the first comprehensive study on a large sample size in Hamadan Province, Iran. In conclusion, the present study significantly increased the spectrum of HBB gene mutations in Hamadan Province compared with previous studies. Therefore, these results can be helpful in identifying β-thal carriers and at-risk fetuses through prenatal diagnosis (PND).     

Characterization of the HBB: c.*233G > C Variant: No Evidence of a β-Thalassemic Phenotype

β-Thalassemia (β-thal) results from homozygous or compound heterozygous inheritance of β-globin alleles that yield decreased or absent synthesis of the β chain. Disease is frequently severe, requiring lifelong transfusion therapy. Heterozygosity for a β-thal allele results in an asymptomatic carrier state with mild but characteristic hematological findings. More than 200 β-globin alleles have been demonstrated to produce β-thal. For populations with a high prevalence of β-thal, screening for carrier status, genetic counseling and prenatal diagnosis are important components of efforts to both reduce disease incidence and provide early diagnosis and treatment. It is therefore important to define and characterize potential β-thal alleles. We sought to further characterize the previously reported β-thal allele, HBB: c.*233G?>?C. This variant is provisionally included in the HbVar database based on a study of Palestinians in the Gaza Strip with β-thal disease or carrier status (known or suspected) where 4.2% of subjects were found to have HBB: c.*233G?>?C. In our patient population, we detected the HBB: c.*233G?>?C variant in 17.3% of individuals (17 heterozygotes, one homozygote) undergoing β hemoglobin (Hb) gene sequencing at our laboratory over a 25-month period. Hematological parameters were analyzed to determine if these individuals demonstrated findings consistent with inheritance of a β-thal allele. Individuals with the HBB: c.*233G?>?C variant did not demonstrate any abnormalities in hematological parameters characteristic of β-thal carrier state (17 heterozygotes) or clinical evidence of disease (homozygote). Our data demonstrate no evidence for pathogenicity of the HBB: c.*233G?>?C variant but rather demonstrate that this variant is a common benign polymorphism.     

Compound Heterozygosity of β-Thalassemia and the Sickle Cell Hemoglobin in Various Populations of Chhattisgarh State,India

Hemoglobinopathies evolved as a protective mechanism against malaria, which exhibit selective advantage in the heterozygous state. However, in a homozygous recessive condition, it poses a serious socioeconomic burden. Sickle cell anemia is an autosomal recessive hemoglobinopathy associated with erythrocytes sickling, vaso-occlusive crisis (VOC), as well as multi-organ failure and death. The coinheritance of other hemoglobinopathies is known to substantially modulate the clinical manifestation of sickle cell anemia. In the present study, we aimed to analyze the coinheritance of β-thalassemia (β-thal) in Hb S (HBB: c.20A>T) patients. The study includes 918 sickle cell anemia patients from 10 ethnic populations of Chhattisgarh State, India. Complete blood counts (CBCs) and hemoglobin (Hb) high performance liquid chromatography (HPLC) fractionation data were collected from patient record books. We observed Hb S-β-thal in all the analyzed populations. Interestingly, high frequencies of Hb S-β-thal have been observed in Satnami (53.8%), Rawat (47.1%), Gond (35.1%) and Panika (30.6%) populations. Inter-population comparison of hematological parameters [Hb F (p?2 (p?p?=?0.03) and red blood cell distribution width (RDW) (p?相似文献   

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.     

β-Thalassemia Mutations in Jamaica: Geographic Variation in Small Communities

Abstract

Over the last 43 years, surveys of over 200,000 subjects in Jamaica have identified β-thalassemia (β-thal) mutations. In most, these genes were detected at birth in patients with sickle cell-β-thal and so the prevalence and distribution would not be influenced by subsequent clinical course. There were two newborn populations, 100,000 deliveries in the corporate area between 1973-1981 and 84,940 in south and western Jamaica between 2008-2016. A third population, which derived from the Manchester Project in central Jamaica, screened 16,612 secondary school children, aged predominantly 15-19 years, and identified 150 students with the β-thal trait and 11 with sickle cell [Hb S (HBB: c.20A>T)]- or Hb C (HBB: c.19G>A)-β-thal. The latter patients may have been subject to symptomatic selection, but this should not have affected those with β-thal trait. Of the 24 different molecular mutations, β⁰-thal genes accounted for 10.0-27.0% of these groups and most common was IVS-II-849 (A>G) (HBB: c.316-2A>G). Of the β⁺ mutations, seven subjects had severe genes with low levels of β chain synthesis but the majority were benign mutations in the promoter region. The –29 (A>G) (HBB: c.-79A>G) mutation dominated in the newborn study in Kingston, similar to experiences in Guadeloupe and African Americans but the –88 (C>T) (HBB: c.-138C>T) mutation was more common among school students in central Jamaica. Caribbean populations are genetically heterogeneous but variations within different parts of Jamaica is of potential importance for prenatal diagnosis and genetic counseling. This information may also be useful among the large Jamaican diaspora.     

Compound Heterozygosity for Hb Alperton (HBB: c.407C>T) and IVS-I-5 (G>C) (HBB: c.92+5G>C) Mutations Presenting as a Moderate Anemia in an Indian Family

While knowledge of HBB gene mutations is necessary for offering prenatal diagnosis (PND) of β-thalassemia (β-thal), a genotype-phenotype correlation may not always be available for rare variants. We present for the first time, genotype-phenotype correlation for a compound heterozygous status with IVS-I-5 (G>C) (HBB: c.92+5G>C) and HBB: c.407C>T (Hb Alperton) mutations on the HBB gene in an Indian family. Hb Alperton is a very rare hemoglobin (Hb) variant with scant published information about its clinical presentation, especially when accompanied with another HBB gene mutation. Here we provide biochemical as well as clinical details of this variant.     

Analysis of Gene Mutation Types of α- and β-Thalassemia in Fuzhou,Fujian Province in China

Abstract

The aim of this study was to explore the type and distribution of α- and β-thalassemia (α- and β-thal) mutations/deletions in Fuzhou, Fujian Province, People’s Republic of China (PRC). For patients whose mean corpuscular volume (MCV) and mean corpuscular hemoglobin (Hb) (MCH) conforms to the characteristics of thalassemia, gap-polymerase chain reaction (gap-PCR) and PCR-reverse dot-blot assays were used to detect α- and β-thal mutations/deletions. Four hundred and twenty-eight cases of thalassemia were detected in 752 suspected cases of thalassemia, including 248 cases of α-thal (57.9%), 175 cases of β-thal (40.9%), and five cases of compound α/β-thal (1.2%). The major genetic types of α-thal were – –^SEA (Southeast Asian; HBA1) and –α^3.7 (rightward; HBA2) deletions, and the carrier rate was 24.9 and 3.3%, respectively. The major genetic types of β-thal were IVS-II-654 (C>T) (HBB: c.316-197C>T), codons 41/42 (–TTCT) (HBB: c.126_129delCTTT), codon 17 (A>T) (HBB: c.52A>T), codons 27/28 (+C) (HBB: c.84_85insC) and –28 (A>G) (HBB: c.-78A>G), and the carrier rate was 9.8, 7.3, 3.5, 1.1 and 0.8%, respectively. The genotypes of α- and β-thal in Fuzhou (Fujian Province, PRC) are characterized by a wide range of distribution, high carrier rate, genetic diversity and genetic heterogeneity. Therefore, it is necessary to detect the thalassemia mutations in the suspected population of this area.     

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.     

Abnormal Hemoglobins in Gurkhas

Abstract

β-Thalassemia (β-thal) is an inherited blood disorder characterized by reduced or absent synthesis of the β chains of hemoglobin (Hb). Although a number of causative mutations have been reported, here we report two novel mutations detected in Chinese patients. Red blood cell (RBC) indices were indicative of β-thal, but no mutations were detected by routine methods. Sequencing of the β-globin gene uncovered one mutant with a 12?bp deletion (TCTGTGTGCTGG) from codon 111 to codon 115 (HBB: c.335-346del12bp) in exon 3. The other was found to be a nonsense mutation at codon 35 (HBB: c.108?C?>?G). The identification of these novel mutations will facilitate future diagnoses of β-thal caused by either of these mutations and will also be useful for genetic counseling and prenatal diagnosis.     

A Novel Frameshift Mutation at Codon 2 (–T) (HBB: c.9delT) and First Report of Three New β-Globin Mutations From Azerbaijan

Abstract

We identified a novel mutation of β-thalassemia (β-thal) in a heterozygous carrier from Azerbaijan. Phenotypical data and molecular mechanisms of codon 2 (–T) (HBB: c.9delT) was relevant to β⁰-thal. Additionally, we here report two new mutations on the HBB gene, not observed previously, in the local population as well as a non causative promoter mutation –198 (A>G) (HBB: c.-248A>G).     

Coinheritance of α- and β-Thalassemia with a Novel Mutation (HBB: c.268_281delAGTGAGCTGCACTG) in a Chinese Family

We report a novel mutation (HBB: c.268_281delAGTGAGCTGCACTG) in a Chinese proband, who was also an α-thalassemia (α-thal) Southeast Asian (αα/–?–^SEA) deletion carrier and displayed characteristic hematological features of β-thalassemia (β-thal) traits. The proband and carriers in her family presented hematological abnormalities. This novel mutation results in a frameshift and consequently creates a premature stop codon at codon 90 of the HBB gene. Thus, couples at-risk for β-thal should also be tested for this mutation. Double heterozygotes for α- and β-thal are easily misdiagnosed as pure β-thal carriers, which should be noted in the process of risk assessment and counseling.     

β-Thalassemia gene mutations in Antalya,Turkey: results from a single centre study

β-Thalassemia (β-thal) is a common autosomal recessive disorder resulting from over 300 different mutations of the β-globin genes. Our aim was to create a mutation map of β-thal in the province of Antalya, Turkey. In this study, mutation analysis of a total 146 of β-thal patients followed at the Thalassemia Center of the Antalya Education and Research Hospital, Antalya, Turkey, were included. Direct DNA sequence analysis was performed for mutation scanning of the β-globin gene. One hundred and forty-six patients with β-thal including all types were analyzed, and 14 different β-thal mutations were detected. The most frequently seen mutation was HBB: c.93???21G?>?A [IVS-I-110 (G?>?A)] (52.7%), followed by HBB: .c.92?+?6T?>?C [IVS-I-6 (T?>?C)] (14.4%), HBB: c.?80T?>?A [–30 (T?>?A)] (8.2%), HBB: c.315?+?1G?>?A [IVS-II-1 (G?>?A)] (8.2%), which made up 83.1% of the observed mutations. Our results indicate the importance of micromapping and epidemiology studies of thalassemia, which will assist in establishing the national prevention and control program in Turkey.     

Coexistence of Two β-Globin Gene Deletions in a Chinese Girl with β-Thalassemia Minor

This study reports a rare case of β^41/42,Cap/β^A genotype in a girl with β-thalassemia (β-thal) minor. The 13-month-old Chinese proband suffered anemia, diarrhea, stunted growth and emaciation. The routine polymerase chain reaction-reverse dot-blot (PCR-RDB) test result for β-thal mutations indicated that she was a compound heterozygote for β^41/42 and β^Cap. However, the complete blood cell (CBC) test gave the following results: mean corpuscular volume (MCV) 79.8 fL, mean corpuscular hemoglobin (MCH) 19.9?pg, with a Hb A₂ value of 5.66%, suggesting that the proband also was β-thal minor. The proband’s father showed typical microcytic hypochromic anemia characteristics with a decreased MCV and MCH (63.1 fL and 20.9?pg, respectively) and an increased level of Hb A₂ (5.60%), while the proband’s mother had normal levels of MCV, MCH and Hb A₂. The PCR-RDB test result showed her father was also a compound heterozygote for the β^41/42 (HBB: c.126_129delCTTT) and β^Cap (HBB: c.-11_-8delAAAC) mutations and her mother was normal. Finally, DNA sequencing identified that the β^41/42 and β^Cap mutations of the proband were inherited from her father and located on one β-globin gene, suggesting that the proband’s genotype is β^41/42,Cap/β^A.