Impact of annotation error in α-globin genes on molecular diagnosis

Borgio, J. Francis

doi:10.1371/journal.pone.0185270

Cited by 7 publications

(3 citation statements)

References 15 publications

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“…In addition, we observed 93 abnormal hemoglobinopathies. The characterization and annotation of the globin gene mutations/deletions were performed as described in previous studies 9,10 . Geographically, Ceheng presented the highest carrier rate (27.98%, 394/1408), and Anlong showed the lowest rate (5.56%, 3/54).…”

Section: Resultsmentioning

confidence: 99%

Early genetic screening uncovered a high prevalence of thalassemia among 18 309 neonates in Guizhou, China

et al. 2021

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Thalassemia is a common monogenic disease in southwestern China, especially in Guizhou province. In this study, 18 309 neonates were examined for thalassemia. The thalassemia carrier rate was 12.90%, which is associated with geographical regions, with carrier frequencies significantly differing between regions (p < 0.0001). The carrier rates for α‐thalassemia and β‐thalassemia were 8.91% and 3.36%, respectively. There are 22 genotypes identified among 1632 α‐thalassemia cases, and 18 genotypes detected among 615 β‐thalassemia cases. The birthrates of individuals with intermediate thalassemia and β‐thalassemia major were 0.153% and 0.055%, respectively. Methodologically, NGS‐Gap‐PCR is superior to traditional detection methods, with 65 more cases detected by NGS‐Gap‐PCR. Since thalassemia‐rich genotypes were highly prevalent in this region, early detection of thalassemia carriers would be meaningful for genetic counseling and prevention/treatment of thalassemia. NGS‐Gap‐PCR provides a powerful tool for neonate genetic testing and clinical diagnosis of thalassemia, especially in high‐prevalence regions.

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Section: Resultsmentioning

confidence: 99%

Early genetic screening uncovered a high prevalence of thalassemia among 18 309 neonates in Guizhou, China

et al. 2021

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“…Another variation in alpha‐1 gene, a C > G in −24 position, in the promoter region (MF970420) also was found in this study. Although this variation is not reported in HB Var or other databases as a mutation, it was mentioned earlier in previous studies as a variant …”

Section: Resultsmentioning

confidence: 69%

Alpha‐globin gene mutation spectrum in patients with microcytic hypochromic anemia from Mazandaran Province, Iran

Hashemi‐Soteh

Karami

Mousavi³

et al. 2019

Clinical Laboratory Analysis

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Background:It is estimated about 7% of the world population is carriers of hemoglobin diseases. Alpha-thalassemia is one of the most common hereditary hemoglobin disorders in the world. This study investigated alpha-globin mutations in potential carriers with hypochromic and microcytic anemia from Mazandaran, in northern Iran. Methods:A total of 859 subjects were selected; genomic DNA was extracted and examined for the presence of mutations in the alpha-globin genes.Results: Mutation analysis of alpha-globin genes revealed 27 different mutations.Seven variants were seen in 91.45% of all alpha-1 and alpha-2 mutations among patients in this study. The 3.7 kb deletion is the most frequent mutation with a frequency of 49.53%, followed by PolyA2 (15.19%), −4.2 deletion (8.76%), --MED (5.84%), IVSI-5nt deletion (5.49%), Hb constant spring (3.62%), and Cd 19 (−G; 3.04%), respectively. There are also seven new variants which were reported for the first time either in alpha-1 or alpha-2 genes, including codon 9 (C > A; α2), deletion of codon 60 (AAG deletion; α2), duplication of codon 94-100 plus 3 base pairs of intron 2 (IVSII + 3; α1), codon 99 (C > A; α2), codon 108 (A > G; α2), codon 128 (A > T; α2), and codon 129 (T > G; α2), respectively. The MLPA method also revealed three rare and novel deletions in alpha-cluster region with about 30 kilobases long. Conclusion:This study showed an efficient identification of α-thalassemia can be achieved using standard hematological indices in our population. The details of these variations will help local genetic services for diagnostic and prenatal diagnosis services. K E Y W O R D S alpha-thalassemia, Iran, Mazandaran, mutation, thalassemiaThis is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

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“…This variant was observed to be frequent in South Asians. The sample having this c.-24C>G variant might be the sample with HBA12 conversion 33 , 34 . The HBA2: c.*107A>G variant is new to be reported in the Pakistani population but previously detected in Albanian patients 35 .…”

Section: Discussionmentioning

confidence: 99%

Mutational analysis of hemoglobin genes and functional characterization of detected variants, through in-silico analysis, in Pakistani beta-thalassemia major patients

Ejaz,

Abdullah,

Usman

et al. 2023

Sci Rep

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Thalassemia is one of the most prevalent genetic disorders worldwide. The present study aimed to explore the mutational spectrum of all hemoglobin (HB) encoding genes and to identify the potentially damaging and pathogenic variants in the beta (β)-thalassemia major patients and thalassemia minor carriers of Southern Punjab, Pakistan. A total of 49 β-thalassemia major patients and 49 carrier samples were screened for the identification of HBA1, HBA2, HBB, HBD, HBE1, HBG1 and HBG2 variants by NGS. PCR was performed for the amplification of HB encoding genes and the amplified product of 13 patients and 7 carrier samples were processed for the Sanger sequencing. Various bioinformatics tools and databases were employed to reveal the functional impact and pathogenicity potential of the observed variants. Results depicted a total of 20 variants of HB-related genes by NGS and 5 by Sanger sequencing in thalassemia patients. While 20 variants by NGS and 3 by Sanger were detected in carriers. Few known genetic variants of HB-encoding genes are being reported for the first time in Pakistani thalassemia patients and carriers. However, two novel HBB variants c.375A>C (p.P125P) and c.*61T>G and a novel variant of HBE1 (c.37A>T (p.T13S)) were also documented. Pathogenicity analysis predicted the pathogenic potential of HBB variants (c.47G>A (p.W16*), c.27-28insG (p. S10fs), and c.92+5G>C) for β thalassemia. The study of functional impact indicated that these HBB variants result in the premature termination of translation leading to the loss of functional β-globin protein. It is therefore suggested that the pathogenic HBB variants, identified during present study, can be employed for the diagnosis, carrier screening, and planning therapy of thalassemia.

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Impact of annotation error in α-globin genes on molecular diagnosis

Cited by 7 publications

References 15 publications

Early genetic screening uncovered a high prevalence of thalassemia among 18 309 neonates in Guizhou, China

Early genetic screening uncovered a high prevalence of thalassemia among 18 309 neonates in Guizhou, China

Alpha‐globin gene mutation spectrum in patients with microcytic hypochromic anemia from Mazandaran Province, Iran

Mutational analysis of hemoglobin genes and functional characterization of detected variants, through in-silico analysis, in Pakistani beta-thalassemia major patients

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