Characterization of Hb Lepore Variants in the UK Population

Guo, Lijia; Kausar, Anika; Old, John; Henderson, Shirley; Gallienne, Alice

doi:10.3109/03630269.2014.988347

Cited by 10 publications

(8 citation statements)

References 17 publications

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“…Five variants of Hb Lepore have been reported due to different gene deletion breakpoints. All these variants were found in different areas, such as Hb Lepore-Hollandia (HGVS: NG_ 000007.3: g.63290_70702del), which has been reported in people of southern and southeast Asia, with rare occurrences being observed in Europe [12].…”

Section: Introductionmentioning

confidence: 99%

Molecular epidemiology and hematologic characterization of δβ-thalassemia and hereditary persistence of fetal hemoglobin in 125,661 families of greater Guangzhou area, the metropolis of southern China

Jiang

Zuo

et al. 2020

BMC Med Genet

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Background: Individuals with δβ-thalassemia/HPFH and β-thalassemia usually present with intermedia or thalassemia major. No large-scale survey on HPFH/δβ-thalassemia in southern China has been reported to date. The purpose of this study was to examine the molecular epidemiology and hematologic characteristics of these disorders in Guangzhou, the largest city in Southern China, to offer advice for thalassemia screening programs and genetic counseling. Methods: A total of 125,661 couples participated in pregestational thalassemia screening. 654 subjects with fetal hemoglobin (HbF) level ≥ 5% were selected for further investigation. Gap-PCR combined with Multiplex ligation dependent probe amplification (MLPA) was used to screen for β-globin gene cluster deletions. Gene sequencing for the promoter region of HBG1 /HBG2 gene was performed for all those subjects. Results: A total of 654 individuals had hemoglobin (HbF) levels≥5, and 0.12% of the couples were found to be heterozygous for HPFH/δβ-thalassemia, including Chinese G γ ( A γδβ) 0 -thal, Southeast Asia HPFH (SEA-HPFH), Taiwanese deletion and Hb Lepore-Boston-Washington. The highest prevalence was observed in the Huadu district and the lowest in the Nansha district. Three cases were identified as carrying β-globin gene cluster deletions, which had not been previously reported. Two at-risk couples (0.0015%) were required to receive prenatal diagnosis. We also found 55cases of nondeletional-HPFH (nd-HPFH), including 54 with Italian nd-HPFH and one with the A γ-197C-T heterozygous state. It is difficult to discriminate between Chinese G γ ( A γδβ) 0 -thal and Italian nd-HPFH carriers using hemoglobin (Hb) analysis. (Continued on next page)Conclusions: This study is the first to describe the familial prevalence of HPFH/δβ-thalassemia and the high-risk rate in Greater Guangzhou Area, and the findings will support the implementation of thalassemia screening for three common deletions by gap-PCR. We also presented a systematic description of genotype-phenotype relationships which will be useful for genetic counseling and prenatal diagnostic services for β-thalassemia intermedia.

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Section: Introductionmentioning

confidence: 99%

Molecular epidemiology and hematologic characterization of δβ-thalassemia and hereditary persistence of fetal hemoglobin in 125,661 families of greater Guangzhou area, the metropolis of southern China

Jiang

Zuo

et al. 2020

BMC Med Genet

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“…Hb Lepore carriers exhibit a β-thalassemia trait phenotype with microcytosis and hypochromia, which result from the decreased transcription of the δβ-hybrid chain. In the United Kingdom, the Antenatal Screening Program guidelines require genetic testing for Hb Lepore and providing genetic counseling to couples at risk of having a child affected with a clinically significant form of thalassemia ( Guo et al, 2015 ). However, Hb Lepore is not included in the routine carrier screening of thalassemia in China.…”

Section: Discussionmentioning

confidence: 99%

Identification of rare thalassemia variants using third-generation sequencing

et al. 2023

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Routine PCR, Sanger sequencing, and specially designed GAP-PCR are often used in the genetic analysis of thalassemia, but all these methods have limitations. In this study, we evaluated a new third-generation sequencing-based approach termed comprehensive analysis of thalassemia alleles (CATSA) in subjects with no variants identified by routine PCR, Sanger sequencing, and specially designed GAP-PCR. Hemoglobin testing and routine PCR tests for 23 common variants were performed for 3,033 subjects. Then, Sanger sequencing and specially designed GAP-PCR were performed for a subject with no variants identified by routine PCR, no iron deficiency, and positive hemoglobin testing. Finally, the new CATSA method was conducted for the subjects with no variants identified by Sanger sequencing and specially designed GAP-PCR. In the 49 subjects tested by CATSA, eight subjects had variants identified. Sanger sequencing and independent PCR confirmed the CATSA result. In addition, it is the first time that Hb Lepore was identified in Hunan Province. In total, traditional methods identified variants in 759 of the 3,033 subjects, while CATSA identified additional variants in eight subjects. CATSA showed great advantages compared to the other genetic testing methods.

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“…In the UK where Indians comprise of the second highest non‐British nationals (~2%), making them the single largest ethnic minority population, investigating 127 δ alleles in patients over 10 years, 58 Hb Lepore heterozygotes were characterized and majority of them (79%) had Hb Lepore Boston Washington. Few individuals with Hb Lepore Hollandia, Hb Lepore Baltimore, and one individual with Hb Lepore ARUP was also reported . Although we picked up 209 individuals with a high HbF determinant, it was often difficult to differentiate δβ thalassemia carriers from HPFH carriers because of their overlapping phenotypes.…”

Section: Discussionmentioning

confidence: 99%

“…29 Lepore ARUP was also reported. 30 Although we picked up 209 individuals with a high HbF determinant, it was often difficult to differentiate δβ thalassemia carriers from HPFH carriers because of their overlapping phenotypes. Genotyping was done in such cases when they were referred for prenatal diagnosis or specifically for molecular typing.…”

Section: Discussionmentioning

confidence: 99%

The phenotypic and molecular diversity of hemoglobinopathies in India: A review of 15 years at a referral center

Nadkarni

Gorakshakar

Sawant

et al. 2018

Int J Lab Hematology

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Introduction The hemoglobinopathies pose a significant health burden in India. Apart from the β thalassemias and sickle cell disorders, α thalassemias and structural hemoglobin variants are also common. Here we have reviewed the phenotypic and molecular diversity of hemoglobinopathies encountered at a referral center in western India over a period of 15 years. Materials and Methods Screening for hemoglobinopathies was done using HPLC and cellulose acetate electrophoresis. Molecular characterization was done using Covalent Reverse Dot Blot Hybridization (CRDB), Amplification Refractory Mutation System (ARMS), GAP PCR and direct DNA sequencing. Results The study includes 31 075 individuals who were referred for diagnosis of hemoglobinopathies and prenatal diagnosis. Of these 14 423 individuals showed various hemoglobin abnormalities. Beta genotyping in 5615 individuals showed the presence of 49 β thalassemia mutations. 143 β thalassemia heterozygotes had normal or borderline HbA2 levels. We identified three δ gene mutations (HbA2 Pellendri, HbA2 St.George, HbA2 Saurashtra) in β thalassemia heterozygotes leading to normal HbA2 levels. The commonest defects among the raised Hb F determinants were Gγ(Αγδβ)0 Indian inversion and the HPFH‐3 Indian deletion. A total of 312 individuals showed the presence of α thalassemia, of which 12.0% had a single α gene deletion (−α/αα). HbH disease was identified in 29 cases with 10 different genotypes. Alpha globin gene triplication was seen in 2.1% of β thalassemia heterozygotes with a thalassemia intermedia phenotype. Seven unusual α chain variants and eight uncommon β chain variants were identified. Conclusion The repertoire of molecular defects seen in the different globin genes will be valuable for management and control of these disorders both in India as well as in other countries where there is a huge influx of migrant populations from India.

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Characterization of Hb Lepore Variants in the UK Population

Cited by 10 publications

References 17 publications

Molecular epidemiology and hematologic characterization of δβ-thalassemia and hereditary persistence of fetal hemoglobin in 125,661 families of greater Guangzhou area, the metropolis of southern China

Molecular epidemiology and hematologic characterization of δβ-thalassemia and hereditary persistence of fetal hemoglobin in 125,661 families of greater Guangzhou area, the metropolis of southern China

Identification of rare thalassemia variants using third-generation sequencing

The phenotypic and molecular diversity of hemoglobinopathies in India: A review of 15 years at a referral center

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