Potensi Penggunaan Materi Genetik Fetus pada Sirkulasi Maternal untuk Diagnosis Prenatal Noninvasif Penyakit Genetik

Diagnosis prenatal adalah teknik diagnostik untuk menentukan kondisi fetus yang belum lahir apakah memiliki kelainan genetik ataupun kelainan lainnya. Teknik ini umumnya dilakukan pada penyakit genetik yang tidak dapat diobati di mana terminasi menjadi bahan pertimbangan. Teknik ini juga dilakukan pada kasus yang memerlukan penanganan segera pada saat prenatal dan pada kondisi yang dapat menimbulkan morbiditas atau mortalitas pada ibu. Diagnosis prenatal dapat dilakukan melalui metode invasif dan noninvasif. Metode invasif seperti amniocentesis dan biopsi villi korialis (CVS) memiliki resiko menimbulkan kecacatan bahkan kematian fetus. Pendekatan nonivasif melalui ultrasonografi belum cukup akurat untuk diagnosis penyakit genetik, sehingga masih memerlukan pengambilan sampel fetus untuk menegakkan diagnosis. Pendekatan terbaru pengambilan sampel fetus secara noninvasif dilakukan melalui pengambilan sel fetus, DNA dan mRNA fetus yang terdapat dalam sirkulasi darah maternal. Pada artikel ini dipaparkan mengenai perkembangan riset, kendala, serta potensi aplikasi klinis ketiga metode pengambilan sampel fetus tersebut.Kata kunci: diagnosis prenatal nonivasif, penyakit genetik, cell-free fetal DNA/mRNA, sel fetus.  [Potential Use of Fetal Genetic Material in Maternal Circulation for Prenatal Noninvasive Diagnosis of Genetic Disease].Prenatal diagnostic technique is used to determine whether the unborn fetus is affected with a genetic disorder or other abnormality. This technique is generally carried out for a genetic disease that is not treatable, in which the termination should be considered. This technique is also performed in cases that require immediate action during the prenatal period and in conditions that can lead to morbidity or mortality of the mother. Prenatal diagnosis can be done by invasive and noninvasive methods. Invasive methods such as amniocentesis and chorionic villus sampling (CVS) have a risk of causing disability and even death of the fetus. While noninvasive approach by ultrasound is not sufficiently accurate for the diagnosis of genetic diseases, therefore further  fetal sampling is required. Noninvasive prenatal diagnosis is a new type of genetic testing done through taking fetal cells, fetal DNA and mRNA, which are found in maternal blood circulation. In this review, we present development of research, constraints, and potential clinical applications of these three methods for noninvasive sampling of the fetus.Keywords: noninvasive prenatal diagnosis, genetic disease, cell-free fetal DNA/mRNA, fetal cell

Frequency of thalassemia carrier and Hb variant and the quality of stored donor blood

Background: This study was aimed to determine the frequency of thalassemia and Hb variant in blood donor. In addition, we also wanted to know the quality of blood from the donor up to seven days of storage, by calculating percentage of hemolysis in vitro.Methods: This cross-sectional study was conducted on 138 blood donor specimens at Red Cross Blood Centre Unit in Jakarta. All specimens were tested for thalassemia and Hb variant by complete blood count (CBC) and Hb analysis with HPLC method and DNA analysis for the detection of α thalassemia carrier. To analyze the quality of stored blood, the calculation of hemolytic rate of red blood cells (RBCs) on whole blood (WB) was compared between the first and seventh days of storage.Results: Out of the 138 specimens, 5 samples (3.6%) were diagnosed for α thalassemia carrier in which, one of them is co-inherited with ovalositosis hereditary (Southeast Asian Ovalositosis/SAO), 3 samples (2.2%) for β thalassemia carrier, and 3 samples (2.2%) for Hb E. Meanwhile, the hemolytic rates of RBCs on WB in first day and seven day of storage were below one percent.Conclusion: The frequency of thalassemia carrier and Hb variants in blood donors at Red Cross Blood Centre Unit in Jakarta was 8%. The quality of stored blood until seven day of storage was quite good.</p

Detection of Papua New Guinea Thalassemia Alpha Mutation in Gayo, Sumba, Ternate, and Timika Populations

Abstract &nbsp; Papua New Guinea (PNG) mutation is a point mutation that occurs in noncoding region of alpha globin clusters. Polymorphism promotes an additional recognition site for transcription factor (GATA-1) which presumably downregulates alpha globin synthesis. The aim of this research is to detect PNG mutation in other populations in Indonesia, thus the results will be used for completing standard diagnoses in detecting alpha thalassemia mutation based on ethnic background. The method used in detecting PNG mutation was PCR-RFLP. Detection of 399 samples (MCH &lt;80 fL) using the PCR-RFLP method showed positive results for the Timika population. However, negative results were found in the Gayo, Sumba, and Ternate populations. PNG mutation frequency in the Timika (Papuan ethnic) population is 18.1% (28 of 154 samples). High malaria prevalence in East Indonesia did not show a positive correlation with the absence of PNG mutation in the Sumba and Ternate populations. The results showed that PNG mutation is only found groups that are infected with Plasmodium falciparum malaria, but not in Plasmodium vivax-infected ones. However, PNG mutation is common in the eastern Indonesia population. &nbsp; &nbsp; Abstrak &nbsp; Deteksi Mutasi Papua Nugini (PNG) Thalassemia Alfa di Populasi Gayo, Sumba, Ternate, dan Timika. Mutasi PNG merupakan mutasi titik di luar gugus globin alfa. Polimorfisme menyebabkan terbentuknya promoter baru sebagai situs pengikatan faktor transkripsi GATA-1 yang diduga menurunkan laju transkripsi normal globin alfa. Tujuan dari penelitian ini adalah untuk mengetahui keberadaan mutasi PNG di populasi lain di Indonesia, sehingga hasil penelitian ini dapat digunakan untuk melengkapi standar diagnosis dalam mendeteksi mutasi penyebab thalassemia alfa berdasarkan latar belakang etnik. Teknik yang digunakan dalam mendeteksi mutasi PNG adalah PCR-RFLP. Hasil menunjukkan 18,1% (28 dari 154 sampel) positif pada populasi Timika, namun hasil negatif ditunjukkan pada semua sampel DNA populasi Gayo, Sumba, dan Ternate. Prevalensi malaria yang tinggi di wilayah Indonesia Timur tidak menunjukkan korelasi positif terhadap keberadaan mutasi PNG di populasi Sumba dan Ternate. Hasil penelitian menunjukkan bahwa mutasi PNG ditemukan hanya pada kelompok individu yang terinfeksi Plasmodium falciparum tetapi tidak pada kelompok individu yang terinfeksi Plasmodium vivax dan mutasi PNG juga ditemukan pada satu individu beretnik Ambon yang tinggal di Timika. &nbsp

Detection of Papua New Guinea Thalassemia Alpha Mutation in Gayo, Sumba, Ternate, and Timika Populations

AbstractPapua New Guinea (PNG) mutation is a point mutation that occurs in noncoding region of alpha globin clusters. Polymorphism promotes an additional recognition site for transcription factor (GATA-1) which presumably downregulates alpha globin synthesis. The aim of this research is to detect PNG mutation in other populations in Indonesia, thus the results will be used for completing standard diagnoses in detecting alpha thalassemia mutation based on ethnic background. The method used in detecting PNG mutation was PCR-RFLP. Detection of 399 samples (MCH5 hlm