الفهرس 
? List of AbbreviationsOnly 14 pages are availabe for public view
 |  | from | 249 |  |  |
| | | from | 249 | | |
Abstract
β-thalassemiais one of the commonest autosomal recessive diseases with a high frequency in population of the Mediterranean area, Middle East, Indian subcontinent, Far East, Tropical Africa,and the Caribbean .
β-thalassemia is a genetic hereditary disorder characterized by the decrease or absence of β-globin chain production due to mutations in coding and non - coding sequences of the β-globin gene
The presence of circulating cell-free DNA (cf-DNA) of fetal and placental origin in maternal plasma has allowed the development of non invasive tools to detect fetal genetic abnormalities from a maternal blood draw .
The development of noninvasive tools for these disorders is important, as it allows patients and doctors to make informed decisions in pregnancies at risk of severe conditions while reducing anxiety related to invasive or postnatal testing.
The aim of this study was to evaluate investigation used in the detection of inherited mutation of beta-thalassemia in maternal plasma during pregnancy and evaluate the diagnostic test performance of cell free fetal DNA for this issu.
A total of 18 papers were obtained using the mentioned keywords in the research of all internet-based databases.
The date of publication was from 2013 to 2017.
The total number of cases in all of the studies was 530 cases
Different methods are suggested for detection of cff-DNA in maternal plasma. Allele-specific real-time PCR is the first approach that was used to detect paternal mutations in maternal plasma. On the other hand, some authors employed digital size selection and investigated relative mutation dosage (RMD) , melting curve analysis (MCA), Primer-Introduced Restriction Analysis Polymerase Chain Reaction , COLD-PCR and microarray and PCR-RFLP-based linkage analysis for detection of paternal mutation in maternal circulation .
Recent advances in the development of new technologies led to detection of both paternal and maternal mutations. Also, a genome-wide map of the fetus has been generated for the parental haplotypes. Haplotype analysis and targeted nextgeneration sequencing provide NIPD for thalassemia (alpha and beta) by identifying paternal mutation in maternal plasma .
Next-generation sequencing also termed Bdeep sequencing, whereby the whole genomic template is fragmented, sequenced in short reads, and then reassembled throughout complex bioinformatics judgment with a genomic database.
Also, digital PCR is a highly sensitive method for quantifying f-DNA in maternal plasma and could be used to detect mutations present at low level of f-DNA in samples to be analyzed .
Overall, 8 % misdiagnosis rate for detection of paternal mutation in maternal serum is due to low quantity of DNA .
Detection of paternal allele in maternal plasma is possible, but, in couples with different mutations. If paternal allele is present in maternal plasma, the probability of the fetus having thalassemia major is 50 %, so it is necessary to perform invasive procedure.
If the absence of paternally inherited mutation is reported in maternal plasma, the mother would rule out the risk of having an affected fetus; thus, this case could be excluded from further invasive prenatal diagnosis screening. This simple analysis can reduce the need for performing invasive prenatal diagnosis by 50 %. Also, we suggest if the initial result of maternal plasma DNA analysis is negative for the presence of paternal mutation, the test be repeated in the second trimester of pregnancy before implies invasive procedure already been carried out.
The drawback of this method is that it cannot determine whether a fetus has a thalassemia major or inherited maternal mutation. The limitations of this study were not being able to make use of papers in different languages apart from Persian and English, and articles that were not open access.
Conclusion
detection of paternal allele in maternal circulation by detection of cell free fetal DNA is feasible. Nevertheless, more studies are required for developing and validating methods into efficient, precise, and reliable assays for detection paternally mutation in maternal plasma.
Recent advances in the development of new technologies led to detection of both paternal and maternal mutations. Also, a genome-wide map of the fetus has been generated for the parental haplotypes. Haplotype analysis and targeted next generation sequencing provide NIPD for thalassemia (alpha and beta) by identifying paternal mutation in maternal plasma .
Next generation sequencing (NS) is the best method for detection of cff-DNA in maternal circulation as regard specifity, sensitivity ,cost and simplicity until now.