Molecular characterization of mutations causing β -thalassemia in Faisalabad Pakistan using the amplification refractory mutation system (ARMS-PCR)

Baig, Shahid Mahmood; Rabbi, Fazli; Hameed, Uzma; Qureshi, J.A.; Mahmood, Zaid Jamal; Bokhari, S. Nazim Hussain; Kiani, Ali Asghar; Hassan, Hammad; Baig, JM; Azhar, Aisha; Zaman, Tariq

doi:10.4103/0971-6866.16806

Cited by 12 publications

(5 citation statements)

References 12 publications

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“…However, these variants have also been examined in carriers worldwide but not reported in Pakistani carriers. The HBB: c.27_28insG (p. Ser10Valfs*14) variant detected in our carriers was observed in another study with (39.1%) frequency in the fetus during prenatal diagnosis in South Punjab and is considered as the second most observed variant (37.3%) in Pakistani thalassemia patients 18 , 21 . This variant is known to be among the most common variants detected in different provinces of Pakistan i.e., Punjab, Sindh and KPK with (31.70%) allele frequency 22 .…”

Section: Discussionsupporting

confidence: 67%

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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Section: Discussionsupporting

confidence: 67%

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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“…13,14 Consanguinity and low literacy rate accounts for highest contributory factor (more than 81%) for the risk factors for high incidence of thalassemia in South Punjab. 15 Cultural beliefs and misinterpretation of religious commands by the general population has resulted in increasing rate of thalassemia prevalence in our country. 16 Pakistan is developing country with per capita income $1380.…”

Section: Introductionmentioning

confidence: 99%

Knowledge of thalassemia and consanguinity: A multicenter hospital based retrospective cohort study from metropolitan city of Karachi, Pakistan.

Khalid

Noreen

Qureshi

et al. 2019

TPMJ

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Objectives: To find the association between consanguinity and frequency of b-thalassemia and to assess the knowledge of parents regarding disease as well as inclination towards premarital carrier screening (PMCS), pre natal diagnosis, pre conception genetic counseling. Study Design: A retrospective cohort study. Setting: Patients with beta thalassemia attending Fatimid Foundation and PNS Shifa Hospital, Karachi. Period: Six Months July – December, 2017. Materials and Methods: Data was collected by pre tested questionnaire which include basic demographic profile, frequency of consanguineous marriages and knowledge regarding disease from parents of children suffering from thalassemia. The study was approved by ethical review committee. Data was analyzed using SPSS version 21. Chi square test was applied. Results: Data was collected from 200 study participants including parents of thalassemia. Males were 52% and 48% were the females. 78.5% were relatives (p=0.001) out of these related, first degree relatives were 61% and 17.5% were distant relatives (p 0.009). Only 25% were aware of genetic counseling, 65% know that thalassemia had genetic mode of transmission (p=0.005), 24% were aware of screening modalities available for thalassemic patients (p=0.001). About 63.55% agreed that premarital screening can prevent thalassemia (p=0.001), majority (83%) of parents were not aware of pre natal diagnosis of thalassemia (p=0.001) more than half of study participants (52%) were still in favor of cousin marriages in future. Conclusion: Thalassemia was found most prevalent among first degree familial relatives. Parents have inadequate knowledge regarding disease. Lack of knowledge and trends consanguineous marriages are strong contributory factor for causation of disease.

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“…In addition, lack of awareness is another persistent problem which has resulted in increased number of thalassemia cases in Pakistan. As a result, most of the children are born with this disease which reduces the chances to control it before birth (Baig et al, 2005). A new strategy developed for proper screening of the infected or doubtful families include index case or retrospective inductive screening (Old, 2003), which is economical, feasible and more practicable than other screening methods in Pakistan.…”

Section: Resultsmentioning

confidence: 99%

Monitoring Molecular Heterogeneity of β-thalassemia Syndrome in District Nowshehra

Shakeel¹,

Ishfaq²,

Rehman³

et al. 2016

Science, Technology and Development

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Among the reported single gene disorders/syndrome, hemoglobin infection is the most common and widespread genetic disorder. Thalassemia arises from defect in red blood cell proteinaceous component (hemoglobin), which carries oxygen and may lead to anemia. Present study aimed to detect the common molecular abnormalities of β-thalassemia syndrome in district Nowshehra, Khyber Pakhtunkhwa, Pakistan. This work was conducted at Abdul Wali Khan University, Mardan, the reports collecting blood samples from patients (average age 13 years) and their families with β-thalassemia major (n = 13 families) belonged to district Nowshehra. The assembled blood samples from the patients were tested for the presence of most common mutations, using Polymerase Chain Reaction (PCR). This study reports six known mutations (IVS-1-5, FSC 8/9, CD 41/42, IVS-1-1, CD 15 and FSC-5) comprising 90% of the total β-thalassemia genes in Pakistan. In our study, IVS 1-5 and FSC-8/9 were the most widespread β-thalassemia gene mutation detected in patients belonging to district Nowshehra. The findings of the study can be used to get an idea about the most common mutation in this region and in designing pre-natal programmes to control the genetic disease.

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Molecular characterization of mutations causing β -thalassemia in Faisalabad Pakistan using the amplification refractory mutation system (ARMS-PCR)

Cited by 12 publications

References 12 publications

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

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

Knowledge of thalassemia and consanguinity: A multicenter hospital based retrospective cohort study from metropolitan city of Karachi, Pakistan.

Monitoring Molecular Heterogeneity of β-thalassemia Syndrome in District Nowshehra

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