Hemophilia A and B, inherited as X-linked recessive traits, are the most common hereditary hemorrhagic disorders caused by a deficiency or dysfunction of coagulation factor VIII (FVIII) or FIX, respectively. Hemophilia is prevalent worldwide, without ethnic or geographic limitations, and remains a life-threatening and often disabling condition. Advances in molecular medicine in this century have markedly improved hemophilia treatment. However, management is still largely inadequate in developing countries. Therefore, carrier detection and prenatal diagnosis remain the key steps for the prevention of the birth of children with hemophilia in developing countries where patients with this coagulation disorder rarely live beyond childhood. Carrier detection and prenatal diagnosis are possible by direct or indirect genetic analysis of the F8 or F9 genes. In countries with more advanced molecular facilities and higher budget resources, the most appropriate choice in general is a direct strategy for mutation detection by prescreening techniques or direct mutation detection. However, in countries with limited facilities and low budget resources, carrier detection and prenatal diagnosis are usually performed by linkage analysis with genetic markers. This article suggests the possibilities of genetic diagnosis and a feasible strategy for carrier detection and prenatal diagnosis in families with hemophilia A and B in developing countries.

Carrier detection and prenatal diagnosis of hemophilia in developing countries.

Summary. Haemophilia A is an X-linked inherited bleeding disorder. Linkage diagnosis using polymorphic markers in the factor VIII gene is used to archive the carrier detection and prenatal diagnosis. The objective of this study was to establish the allele frequency and heterozygosity rate (HR) of two new intragenic markers (Intron 1 and 24) and other markers (Intron 13 and 22) using fluorescent PCR. Five hundred unrelated healthy women were screened and haemophilic family was studied for carrier detection and prenatal diagnosis. We observed five different alleles of Intron 1, 10 of Intron 24, nine of Intron 13 and six of Intron 22. The observed HR for Intron 1, 24, 13 and 22 were 34.0, 35.2, 53.0 and 42.6%, while the expected HR were 33.6, 36.3, 50.1 and 44.3%, respectively. Heterozygosity rate with the combined use of all four intragenic markers was 76.6% (383/500). In prenatal diagnosis of a haemophilic family, a pregnant woman was heterozygous with three intragenic (Intron 1, 13 and 22) and one extragenic St14 VNTR (DXS52) markers. She was considered to be a carrier, and she carried a male foetus by AMXY PCR and chromosome analysis of amniocytes. Foetus did not have mutant haplotype as his uncle, suggesting a normal male status. Our study demonstrates the utility of two new intragenic markers in FVIII gene for carrier detection and prenatal diagnosis of haemophilic families.

Identification of new dinucleotide-repeat polymorphisms in factor VIII gene using fluorescent PCR.

The heterogeneous nature of the mutations, the size, and the complexity of the factor VIII gene makes direct mutation analysis in hemophilia A families in India an option that is not very feasible and practical. Thus, carrier screening and prenatal diagnosis of hemophilia A often depends on haplotype analysis using restriction fragment length polymorphisms (RFLP) and short tandem repeat (STR) markers to track the defective factor VIII gene within a family. The main objective of this present study was to assess the utility of using polymerase chain reaction (PCR)-based five polymorphic markers: four intragenic Hind III, Bcl I, intron 13, and intron 22 STRs and one extragenic marker St14 in prenatal diagnosis. Forty-one chorionic villus samples (CVS) were studied from 41 families with a history of hemophilia A. PCR and RFLP were used for screening. Intron 22 STR showed the highest informativeness (60.9%), followed by Hind III (51.2%), Bcl I (46.3%), & intron 13 STR (51.2%); the extragenic marker St14 (VNTR) was informative in 46.3% of families. Linkage analysis, with the combined use of these five PCR-based polymorphic markers, gives good informativeness of 87.8% in the Indian population. Of the 41 CVS tested, 21 were found to be male fetuses and of these 13 were found likely to be affected with hemophilia A. Only in 12.2% of the families were none of the markers informative.

Prenatal diagnosis in hemophilia A using factor VIII gene polymorphism—Indian experience

Linkage analysis is a widely used strategy for genetic counselling in haemophilia A (HA) families. We attempted to develop more informative markers closely linked to factor VIII (FVIII) gene and establish a rapid multifluorescent polymerase chain reaction (PCR) method with these markers. Five extragenic (DXS15, DXS9901, G6PD, DXS1073 and DXS1108) and one intragenic (F8Civs13) markers were examined in 118 healthy individuals and 12 HA families which had been diagnosed before. Five extragenic markers were within an interval of about 1.5 Mb to FVIII gene and located on each side of the gene. The expected heterozygote rate (HR) of DXS15, DXS9901, G6PD, DXS1073, DXS1108 and F8Civs13 were 74.97%, 79.77%, 56.06%, 59.92%, 39.97% and 47.61%, while the observed HR were 88.24%, 82.35%, 21.57%, 62.75%, 35.29% and 52.94%. When six polymorphic markers were combined together, all the studied females were informative in at least one of these markers and 29.41% of them were detected informative in three markers with the highest frequency. The diagnostic rates of DXS15, DXS9901, G6PD, DXS1073, DXS1108 and F8Civs13 in 12 haemophilia families were 75.00%, 91.67%, 41.67%, 75.00%, 33.33% and 66.67% respectively. All the genetic diagnosis was consistent with the result we analysed before and no recombination was observed. Family 1 was given as an example in this study and was found to be informative in three polymorphic markers DXS15, DXS9901 and DXS1073. The patient's sister was detected the same allele as the proband, but her male fetus did not inherit the affected allele from her, which was consistent with the result of sequencing. It was demonstrated that the multifluorescent PCR method established in this study was convenient and efficient and can be applied to carrier detection and prenatal diagnosis in HA families.

A rapid multifluorescent polymerase chain reaction for genetic counselling in Chinese haemophilia A families.

DNA-based diagnosis of haemophilia A has previously been carried out by linkage analysis using two highly informative markers, Hind III RFLP and St14 VNTR, for affected Turkish families. In the present study the number and frequency of the microsatellite alleles at introns 13 and 22 in the factor VIII (FVIII) gene were analysed in order to increase the rate of informative females and accuracy of linkage analysis. Six alleles were observed at both loci. The two most frequent alleles of each locus were the same as the two common alleles found in Anglo-Americans. The comparison of heterozygosity of both microsatellite loci showed that the Turkish population is slightly less polymorphic than Anglo-Americans but more polymorphic than Chinese, Slavs and Uzbekians. The additional use of the two microsatellite repeat polymorphisms with the previously established informative markers has been accepted as the most effective strategy in DNA diagnosis by linkage analysis for the assessment of haemophilia A carriers and affected fetuses in the Turkish population. The modifications adopted in this study for the multiplex PCR analysis of the microsatellite repeat polymorphism eliminated the use of radioactivity and sequencing gels, reducing cost and labour.

Analysis of the two microsatellite repeat polymorphisms of the factor VIII gene in the Turkish population

RFLP analysis of some intra- and extra-genic polymorphic sites of Factor VIII (FVIII) and Factor IX (FIX) genes with relevant DNA probes or by polymerase chain reaction (PCR) was carried out in Slavic populations from the European part of Russia and also in the native ethnic groups of Uzbekistan and Kazahstan. The allele frequencies for the HindIII (intron 19) and XbaI (intron 22) polymorphic sites (PSs) in the FVIII gene were very similar in the two populations studied, but different for the intron 13 (CA)n repeat. Significant variations in the TaqI (intron d) and DdeI (intron a) polymorphisms of the FIX gene were evident between the Russian and Asian populations. Two unusual alleles (4.35 and 4.2 kb) for the extragenic PS St14/TaqI were registered in Slavs and one new allele (380 bp) for the DdeI polymorphic site of FIX was discovered in both Asian populations. Altogether, 210 haemophilia A (HA) and 24 haemophilia B (HB) families were subjected to molecular studies. So far, 160 HA and 12 HB families have been found to be informative for DNA analysis. Carrier status was ascertained in 42 HA and 6 HB female relatives, and rejected in 52 and 10 of them, respectively. The origin of some HA and HB mutations was traced with relevant polymorphic markers in several at-risk families. Prenatal diagnosis was accomplished in 28 HA and three HB families, resulting in the identification of 20 affected male fetuses.

Allele frequencies and molecular diagnosis in haemophilia A and B patients from russia and from some Asian Republics of the former U.S.S.R.

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

L. Papaian

Author Tools

Chat about Author

Papers

Allele frequencies and molecular diagnosis in haemophilia A and B patients from russia and from some Asian Republics of the former U.S.S.R.