Prenatal exclusion of β thalassaemia major by examination of maternal plasma

Chiu, Rossa W.̉K.; Lau, Tze Kin; Leung, Tse Ngong; Chow, Katherine C.K.; Chui, David H.K.; Lo, Y.M. Dennis

doi:10.1016/s0140-6736(02)11086-5

Cited by 245 publications

(143 citation statements)

References 5 publications

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“…This would avoid the small but possible risks of fetal injury or even fetal loss during invasive methods including amniocentesis and chorionic villus sampling. An early report of the use of maternal peripheral blood sampling for prenatal diagnosis of thalassemia was published in 2002 [13]. However, this report only screened for one particular mutation which was relatively easy to detect.…”

Section: Diagnosis: From Protein To Genes To Prenatal Diagnosismentioning

confidence: 99%

Thalassemia 2016: Modern medicine battles an ancient disease

Rund

2015

American J Hematol

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Thalassemia was first clinically described nearly a century ago and treatment of this widespread genetic disease has greatly advanced during this period. DNA‐based diagnosis elucidated the molecular basis of the disease and clarified the variable clinical picture. It also paved the way for modern methods of carrier identification and prevention via DNA‐based prenatal diagnosis. Every aspect of supportive care, including safer blood supply, more regular transfusions, specific monitoring of iron overload, parenteral and oral chelation, and other therapies, has prolonged life and improved the quality of life of these patients. Significant advances have also been made in allogenic bone marrow transplantation, the only curative therapy. Recently, there has been a rejuvenated interest in studying thalassemia at the basic science level, leading to the discovery of previously unknown mechanisms leading to anemia and enabling the development of novel therapies. These will potentially improve the treatment of, and possibly cure the disease. Pathways involving activin receptors, heat shock proteins, JAK2 inhibitors and macrophage targeted therapy, among others, are being studied or are currently in clinical trials for treating thalassemia. Novel types of genetic therapies are in use or under investigation. In addition to the challenges of treating each individual patient, the longer survival of thalassemia patients has raised considerations regarding worldwide control of thalassemia, since prevention is not universally implemented. This review will trace a number of the original medical milestones of thalassemia diagnosis and treatment, as well as some of the most recent developments which may lead to innovative therapeutic modalities. Am. J. Hematol. 91:15–21, 2016. © 2015 Wiley Periodicals, Inc.

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Section: Diagnosis: From Protein To Genes To Prenatal Diagnosismentioning

confidence: 99%

Thalassemia 2016: Modern medicine battles an ancient disease

Rund

2015

American J Hematol

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“…This method has been readily applied to sex-linked (5) and certain single-gene (6,7) disorders, but its use for fetal chromosomal aneuploidies has been a challenge (4). First, fetal nucleic acids coexist in maternal plasma with a high background of maternal nucleic acids that can often interfere with analysis (8).…”

mentioning

confidence: 99%

Digital PCR for the molecular detection of fetal chromosomal aneuploidy

Lun²,

Chan³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

390

328

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Trisomy 21 is the most common reason that women opt for prenatal diagnosis. Conventional prenatal diagnostic methods involve the sampling of fetal materials by invasive procedures such as amniocentesis. Screening by ultrasonography and biochemical markers have been used to risk-stratify pregnant women before definitive invasive diagnostic procedures. However, these screening methods generally target epiphenomena, such as nuchal translucency, associated with trisomy 21. It would be ideal if noninvasive genetic methods were available for the direct detection of the core pathology of trisomy 21. Here we outline an approach using digital PCR for the noninvasive detection of fetal trisomy 21 by analysis of fetal nucleic acids in maternal plasma. First, we demonstrate the use of digital PCR to determine the allelic imbalance of a SNP on PLAC4 mRNA, a placenta-expressed transcript on chromosome 21, in the maternal plasma of women bearing trisomy 21 fetuses. We named this the digital RNA SNP strategy. Second, we developed a nonpolymorphism-based method for the noninvasive prenatal detection of trisomy 21. We named this the digital relative chromosome dosage (RCD) method. Digital RCD involves the direct assessment of whether the total copy number of chromosome 21 in a sample containing fetal DNA is overrepresented with respect to a reference chromosome. Even without elaborate instrumentation, digital RCD allows the detection of trisomy 21 in samples containing 25% fetal DNA. We applied the sequential probability ratio test to interpret the digital PCR data. Computer simulation and empirical validation confirmed the high accuracy of the disease classification algorithm.circulating fetal nucleic acids ͉ noninvasive prenatal diagnosis ͉ sequential probability ratio test ͉ trisomy 21 ͉ RNA SNP

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“…[17][18][19][20] In view of this limitation, we previously showed that the detection of the paternally inherited SNPs is feasible for the NIPD of b-thalassaemia. 22,23 SNPs can be used regardless of the mutation of the carrier couples, they provide positive detection of the paternal allele, normal or mutant, the result can be confirmed with more than one SNP and, importantly, the more SNPs used the less diagnostic risk.…”

Section: Discussionmentioning

confidence: 99%

“…Allele-specific real-time PCR is one of the first approaches that have been used to exclude paternal mutations in the maternal circulation. 17 Preferential detection of fetal alleles was achieved through initial enrichment of fetal DNA, 8,18 while others enhanced the production of the mutated fetal allele by employing either peptide nucleic acid probes 19 or COLD PCR. 20 In the specific case of b-thalassaemia, MALDI-TOF mass spectrometry has been also investigated.…”

Section: Introductionmentioning

confidence: 99%

Next generation sequencing of SNPs for non-invasive prenatal diagnosis: challenges and feasibility as illustrated by an application to β-thalassaemia

et al. 2013

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b-Thalassaemia is one of the most common autosomal recessive single-gene disorder worldwide, with a carrier frequency of 12% in Cyprus. Prenatal tests for at risk pregnancies use invasive methods and development of a non-invasive prenatal diagnostic (NIPD) method is of paramount importance to prevent unnecessary risks inherent to invasive methods. Here, we describe such a method by assessing a modified version of next generation sequencing (NGS) using the Illumina platform, called 'targeted sequencing', based on the detection of paternally inherited fetal alleles in maternal plasma. We selected four single-nucleotide polymorphisms (SNPs) located in the b-globin locus with a high degree of heterozygosity in the Cypriot population. Spiked genomic samples were used to determine the specificity of the platform. We could detect the minor alleles in the expected ratio, showing the specificity of the platform. We then developed a multiplexed format for the selected SNPs and analysed ten maternal plasma samples from pregnancies at risk. The presence or absence of the paternal mutant allele was correctly determined in 27 out of 34 samples analysed. With haplotype analysis, NIPD was possible on eight out of ten families. This is the first study carried out for the NIPD of b-thalassaemia using targeted NGS and haplotype analysis. Preliminary results show that NGS is effective in detecting paternally inherited alleles in the maternal plasma.

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Prenatal exclusion of β thalassaemia major by examination of maternal plasma

Cited by 245 publications

References 5 publications

Thalassemia 2016: Modern medicine battles an ancient disease

Thalassemia 2016: Modern medicine battles an ancient disease

Digital PCR for the molecular detection of fetal chromosomal aneuploidy

Next generation sequencing of SNPs for non-invasive prenatal diagnosis: challenges and feasibility as illustrated by an application to β-thalassaemia

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