Modifying effect of XmnI, BCL11A, and HBS1L-MYB on clinical appearances

Rujito, Lantip; Basalamah, Muhammad Ridwan; Siswandari, Wahyu; Setyono, Joko; Wulandari, Gondo; Mulatsih, Sri; Sofro, Abdul Salam M.; Sadewa, Ahmad Hamim; Sutaryo, Sutaryo

doi:10.1016/j.hemonc.2016.02.003

Cited by 45 publications

(42 citation statements)

References 39 publications

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“…For example, patients with thalassemia, a disorder caused by defective β-globin synthesis, have diverse clinical characteristics and variable expressivity. A number of factors underlie this phenotypic diversity, including the involvement of numerous modifier genes at other genetic loci that affect the production of β-globin (Rujito et al, 2016). Similarly, DYT1 dystonia patients have a wide spectrum of symptom severity, which reflects the incomplete penetrance of the pathogenic ΔE mutation and the variable expressivity of the disease.…”

Section: Discussionmentioning

confidence: 99%

Whole exome sequencing identifies novel DYT1 dystonia-associated genome variants as potential disease modifiers

Hu¹,

Luxton²,

Lee³

et al. 2020

Preprint

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AbstractBackgroundDYT1 dystonia is a neurological movement disorder characterized by painful sustained muscle contractions resulting in abnormal twisting and postures. In a subset of patients, it is caused by a loss-of-function mutation (ΔE302/303; or ΔE) in the luminal ATPases associated with various cellular activities (AAA+) protein torsinA encoded by the TOR1A gene. The low penetrance of the ΔE mutation (∼30-40%) suggests the existence of unknown genetic modifiers of DYT1 dystonia.MethodsTo identify these modifiers, we performed whole exome sequencing of blood leukocyte DNA isolated from two DYT1 dystonia patients, three asymptomatic carriers of the ΔE mutation, and an unaffected adult relative.ResultsA total of 264 DYT1 dystonia-associated variants (DYT1 variants) were identified in 195 genes. Consistent with the emerging view of torsinA as an important regulator of the cytoskeleton, endoplasmic reticulum homeostasis, and lipid metabolism, we found DYT1 variants in genes that encode proteins implicated in these processes. Moreover, 40 DYT1 variants were detected in 32 genes associated with neuromuscular and neuropsychiatric disorders.ConclusionThe DYT1 variants described in this work represent exciting new targets for future studies designed to increase our understanding of the pathophysiology and pathogenesis of DYT1 dystonia.

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Section: Discussionmentioning

confidence: 99%

Whole exome sequencing identifies novel DYT1 dystonia-associated genome variants as potential disease modifiers

Hu¹,

Luxton²,

Lee³

et al. 2020

Preprint

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“…However, variable response to the drug presents various limitations. Earlier studies on pharmacogenomics mainly dealt with identification of genomic variants in γ‐globin, BCL11A, and HBS1L‐MYB, which might be responsible for the selective response to hydroxyurea treatment . Because so far there is no genomic biomarker on the basis of which hydroxyurea therapy can be adapted for SCD and β‐thalassemia patients, we decided to take a pharmacoproteomics approach.…”

Section: Discussionmentioning

confidence: 99%

“…Earlier studies on pharmacogenomics mainly dealt with identification of genomic variants in γ -globin, BCL11A, and HBS1L-MYB, which might be responsible for the selective response to hydroxyurea treatment. 17,18 Because so far there is no genomic biomarker on the basis of which hydroxyurea therapy can be adapted for SCD and βthalassemia patients, [19][20][21] we decided to take a pharmacoproteomics approach. In the past decade rapid technical developments in tandem MS and label-free quantification have resulted in meaningful understanding of pathological pathways, biomarkers, and drug mechanisms at the proteome level.…”

Section: Discussionmentioning

confidence: 99%

Pharmacoproteomics Profiling of Plasma From β‐Thalassemia Patients in Response to Hydroxyurea Treatment

Zohaib

Ansari

Shamsi

et al. 2018

The Journal of Clinical Pharma

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β-Thalassemia is a genetic disorder caused by defects in the β-globin gene resulting in the absence or reduced synthesis of adult hemoglobin (HbA). Hydroxyurea is an effective drug to increase fetal γ-globin (HbF) expression, replacing the missing adult β-globin. The mechanism of HbF induction by hydroxyurea and improvement in clinical symptoms are still poorly understood. In the present study we performed comparative analysis of plasma proteome in pre- and post-hydroxyurea-treated β-thalassemia major transfusion-dependent children (n = 10, mean age = 3.2 years) as well as responders versus nonresponders to hydroxyurea treatment. Plasma was collected before and after 6 months of hydroxyurea treatment, with patients subcategorized on the basis of their response to hydroxyurea. Among 400 identified proteins using a label-free quantitative proteomics approach, 28 proteins were found to be significantly different in pre- versus post-hydroxyurea-treated groups, with transferrin receptor protein-1 being most downregulated and hemopexin and haptoglobin the most upregulated proteins after treatment. In responder versus nonresponder comparison, 26 proteins were found to be differentially expressed, with carbonic anhydrase 1, hemoglobin subunit γ-1, and peroxiredoxin-2 showing the significant changes. The mechanism of hydroxyurea treatment in β-thalassemia patients appears to be complex, requiring a large sample size and a longer period of treatment to reveal its details.

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“…Anak dengan thalassemia mayor akan membutuhkan penanganan berupa transfusi rutin setiap 2-4 minggu sekali dari usia diagnosis sampai sepanjang hidup mereka. Beberapa mutan pada gen modifier dapat mempengaruhi ketiga kategori yang umum ini (Rujito et al, 2016). Akibat transfusi rutin mereka harus mengkonsumsi obat kelasi besi secara rutin untuk mengeluarkan besi yang menumpuk pada sistem organ mereka.…”

Section: Hasil Dan Pembahasanunclassified

Sosialisasi Thalassemia Kepada Guru Biologi di Banyumas: Upaya Pencegahan Terintegrasi Melalui Kurikulum Sekolah

Rujito

Lestari

Aziz³

et al. 2018

pengabdian

Self Cite

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THALASSEMIA SOCIALIZATION TO BIOLOGY TEACHERS IN BANYUMAS: EFFORT OF INTEGRATED PREVENTION THROUGH SCHOOL CURRICULUM. Thalassemia is a hematologic disease that causes hemoglobin blood defects. As a result, red blood cells become fragile and unable to perform their standard functions. Thalassemia in Indonesia is a quite lot. Recorded data, the carrier traits are about 3-10%, spread across all provinces. Currently, no final treatment can cure this disease altogether. Regular transfusion and iron chelating drugs are still survival of thalassemia patients. Prevention program is one of efficient handling. The pattern of thalassemia gene decline follows the laws of the recessive Mendel. Prevention is done by campaigning premarital screening to married couples or further to younger individuals so they can plan marriages wisely. High School Biology teachers are an essential factor in preventing thalassemia. They can deliver prevention programs through lessons at school. They can also be pioneers in an early self-detection carrier to teenagers before they plan a marriage. Because of its strategic role, the socialization of thalassemia in high school teachers becomes very important.

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Modifying effect of XmnI, BCL11A, and HBS1L-MYB on clinical appearances

Abstract: The XmnI locus, rs11886868, and rs766432 have a modifying effect on HbF and clinical score in HbE/β-thal patients in Indonesia, but not in β-thal patients.

Cited by 45 publications

References 39 publications

Whole exome sequencing identifies novel DYT1 dystonia-associated genome variants as potential disease modifiers

Whole exome sequencing identifies novel DYT1 dystonia-associated genome variants as potential disease modifiers

Pharmacoproteomics Profiling of Plasma From β‐Thalassemia Patients in Response to Hydroxyurea Treatment

Sosialisasi Thalassemia Kepada Guru Biologi di Banyumas: Upaya Pencegahan Terintegrasi Melalui Kurikulum Sekolah

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