Prenatal Diagnosis Of Hemophilia Research Articles

Prominent Mutation of Intron 22 Inversion in Sporadic Hemophilia: Is It Worth the Antenatal Screening?

BackgroundAdequate replacement for patients with hemophilia is costly, especially in countries with limited resources.ObjectiveFactor VIII gene mutations among Thai patients with hemophilia A were analyzed for the most common mutation. The cost-effectiveness of finding one female without family history of hemophilia possessing the most common factor VIII mutation was compared with the cost of treating one patient with hemophilia.MethodsIn all, 109 unrelated patients with hemophilia A, defined as sporadic cases (n=58) and hereditary cases (n=51), were enrolled for genotypic analysis.ResultsIntron 22 inversion was prominently found in 34 sporadic (58.6%) and 27 hereditary (51.9%) cases. The screening for intron 22 inversion among females without family history of hemophilia at antenatal care has been optionally suggested. A female with a positive result will undergo further prenatal diagnosis of hemophilia in her male offspring. On the contrary, a female with a negative test result remains at risk to have a hemophiliac son caused by other factor VIII gene mutations not included in the screening but the risk is not as high as intron 22 inversion. Although the screening of factor VIII mutation among females without family history of hemophilia is against the current practice, it has been initiated due to the inadequate treatment provided to patients with hemophilia in countries with limited resources. The study calculated approximately one female with intron 22 inversion would exist among 17,064 females without family history of hemophilia. The cost of screening (194,870 USD) was much less than that of treating one patient with hemophilia from birth to 40 years of age by the current regimen (378,000 USD).ConclusionImplementing antenatal screening of intron 22 inversion among females without family history of hemophilia is optionally suggested, especially in economically less-developed countries with inadequate treatment service for patients with hemophilia.

Attitudes Toward Prenatal Diagnosis and Pregnancy Management in Carriers of Hemophilia: A Qualitative Analysis Exploring the Views of Carriers in Southern Alberta

Introduction Hemophilia A and B are the most common severe bleeding disorders. Improvements in carrier detection and prenatal diagnosis of hemophilia have practical implications for family planning as well as peri- and antenatal pregnancy management. Access to counselling and testing is heterogeneous. We evaluated the awareness and usage of prenatal genetic counselling, sex determination and procedures to determine fetal hemophilia status over time in carriers of hemophilia at our hemophilia treatment centre (HTC). Methods Carriers of hemophilia A or B were recruited through our HTC. Research was approved by our institutional ethics board approval. An online link was emailed to participants using Research Electronic Data Capture (REDCap) Clinical Research Unit software. Survey questions explored demographics, family members affected and severity, pregnancy history, awareness and utilization of carrier testing, genetic counselling, prenatal diagnostic technologies and terminations. Responses were analyzed by 2 reviewers for basic statistics and to identify themes in a descriptive qualitative design. Results & Discussion 85 hemophilia carriers were identified; 3 were lost to follow up and 34 had missing or incorrect contact information. 48 survey invitations were distributed with 24 responses received (50% response rate). One response was excluded as the participant was not a carrier (spontaneous mutation in her son). 20 complete and 3 incomplete responses were analyzed. Median age was 44 years (28-73), with sons most commonly affected family member (14/23, 61%). 3 participants reported no pregnancies, 2 did not respond and 1 did not list the years of her pregnancies. The majority received genetic counselling from HTC personnel. Table 1. Awareness and utilization of carrier testing, counselling, pregnancy, prenatal technologies and termination. * Denominator represents number of responses **Chorionic villae and/or amniotic fluid testing Responses were analyzed by year of pregnancy: prior to 2000 (n=8) or after 2000 (n=9). No pregnancy dates were given in 6 responses. 100% of participants with pregnancy after 2000 had carrier testing. The majority also received genetic counselling (n=8). Members of this group had access to and utilized prenatal diagnostic technologies; pre-implantation genetic diagnosis (n=1), early prenatal diagnosis (n=2) or invasive testing (n=4). Rationale given included: more time to prepare emotionally (n=3), optimize delivery management (n=2), and as a consideration to terminate pregnancy (n=1). Overall, there was increased but heterogeneous knowledge of available technologies potentially reflecting limited understanding during or ineffectively timed counselling, or limited knowledge by carriers who had completed their families when these technologies became available. Identified categories and themes from text responses include: · Impact of family experience with hemophilia: o Themes: severely affected family members impact family planning and attitudes about hemophilia, prenatal diagnosis does not prompt termination due to improvements in hemophilia care · Impact on medical care: o Themes: early identification may prepare for delivery, concern about overtreatment of carriers during delivery · Impact on psychosocial well-being: o Themes: concern about others' opinions, guilt for having more than one affected child · Need for education: o Themes: importance of collaboration between HTC and health care providers, HTC as the primary source for hemophilia related information Study challenges included limited responses precluding statistical analysis and the ability to submit incomplete responses due to sensitive subject matter. Conclusion Genetic technologies have shown significant advances and now allow early detection of those with hemophilia, including carriers. However, this study shows that experiences and knowledge of these technologies are still widely varied. As a result, hemophilia carriers may benefit from standardized educational materials which may compliment counselling provided by HTCs and may be useful for multigenerational knowledge dissemination. Table 1 Table 1. Disclosures No relevant conflicts of interest to declare.

Prenatally Diagnosed Hemophilia in a Newborn: A Case Report

Hemophilia is the most common inherited coagulation disorder, and approximately one-half of patients are diagnosed as newborns. For prenatal diagnosis of hemophilia A, genetic tests are performed using chorionic villi (biopsy PCR chorionic villi sampling [CVS]) at 10 weeks’ of gestation. The result in this fetus demonstrated an inversion within intron 1 in part for hemophilia A. This male infant, who was his parents’ first offspring, was born after an uneventful pregnancy. An uncle suffered from hemophilia A. This report describes a newborn who was prenatally diagnosed with hemophilia A. The timely diagnosis of hemophilia in a newborn enabled the provision of adequate therapy, which led to a favorable outcome.

Prenatal diagnosis of haemophilia in Sweden now more commonly used for psychological preparation than termination of pregnancy.

The aims of the study were to define the frequency, outcome and reasons for prenatal diagnosis (PND) in Sweden during a 30-year period in order to study trends and changes. The study population, from the Swedish nationwide registry of PND of haemophilia, consisted of 54 women, compromising >95% of all, who underwent PND (n=90) of haemophilia during 1977-2013. PND was performed by amniocentesis (n=10), chorionic villus sampling (n=64) or by analysis of foetal blood (n=16). A total of 27/90 foetuses were found to have haemophilia. Sixteen went to termination and the remaining 11 were born during the end of the study period (2000-2013). Three of 90 pregnancies were terminated due to findings other than haemophilia and 3/90 PNDs led to miscarriage. In the 30 families with known haemophilia, PNDs (n=55) were used in 27/55 cases for 'psychological preparation' and in 23/55 cases with the aim to terminate the pregnancy. A subgroup of women (n=17) who consecutively underwent PND in the years 1997-2010 were further interviewed. For 11/17, being a carrier had a negative effect on the decision to become pregnant, and in 11 cases PND had influenced their decision to conceive. Our study show that PND of haemophilia is stable over time but increasingly used during the last decade as a psychological preparation for having a child with haemophilia as compared to earlier where more terminations of pregnancies were conducted.

Identification and Genetic Analysis of a Factor IX Gene Intron 3 Mutation in a Hemophilia B Pedigree in China.

Objective: Hemophilia B is caused by coagulation defects in the factor IX gene located in Xq27.1 on the X chromosome. A wide range of mutations, showing extensive molecular heterogeneity, have been described in hemophilia B patients. Our study was aimed at genetic analysis and prenatal diagnosis of hemophilia B in order to further elucidate the pathogenesis of the hemophilia B pedigree in China.Materials and Methods: Polymerase chain reaction amplification and direct sequencing of all the coding regions was conducted in hemophilia B patients and carriers. Prenatal diagnosis of the proband was conducted at 20 weeks.Results: We identified the novel point mutation 10.389 A>G, located upstream of the intron 3 acceptor site in hemophilia B patients. The fetus of the proband’s cousin was identified as a carrier.Conclusion: Our identification of a novel mutation in the F9 gene associated with hemophilia B provides novel insight into the pathogenesis of this genetically inherited disorder and also represents the basis of prenatal diagnosis.

Prenatal diagnosis of haemophilia: our experience of 44 cases

Haemophilia A and B (HA, HB) are the most frequent X-linked bleeding diseases; two-thirds of cases are severe. We counselled 51 couples for prenatal diagnosis (PD) of haemophilia. In 7/51 (13.7%) cases, the couple decided not to undergo PD because counselling revealed that they were carriers of a mild form of the disease, while we performed 44 PD for severe HA (36 cases) or HB (8 cases). The indication for PD was a haemophilic child (30/44, 68.2%) or an affected family member (12/44, 27.3%); in two cases the non-carrier mother of isolated haemophilic patients requested PD because of the risk of mosaicism. We completed PD in 43/44 cases; in one case, the prenatal sample was contaminated by maternal DNA; however, molecular analysis revealed the female sex of the foetus. We performed PD for 16 of the 36 couples at risk of HA (44.4%) by analysing the intron (IVS)22 inversion; in 1/36 cases (2.8%) the mother had the IVS1 inversion, and in 8/36 (22.2%) the family mutation was identified by sequencing; in 11/36 (30.6%) cases the family mutation was unknown, and PD was performed by linkage (no recombination nor uninformative cases occurred). For HB, in 6/8 (75.0%) cases, PD was performed by DHPLC or by sequencing; in 2/8 cases we tested intragenic markers (again with no cases of recombination or uninformative families). PD in well-equipped laboratories, and multidisciplinary counselling are an aid to planning reproductive and early therapeutic strategies in families with severe haemophilia.

Prenatal diagnosis of haemophilia B: the Italian experience

This article describes prenatal diagnosis (PND) of haemophilia B (HB) within the framework of Italian haemophilia centres and genetics laboratories. The study details the experience from six haemophilia genetic centres (three in the North, one in the Centre and two in the South of Italy) and summarizes the different techniques used to perform PND of HB during the last 15 years. To date, the Italian HB database includes 373 characterized unrelated patients and their genetic information has permitted the identification of 274 carriers of childbearing age. This database represents the main instrument for timely and precise PND. Sixty-six prenatal diagnoses were performed on 52 HB carriers whose average age at the time was 34 (ranging from 24 to 44 years). In 44 cases, genetic counselling for carrier status determination was performed before pregnancy, while eight were not studied prior to pregnancy. Foetal samples were obtained by chorionic villus sampling in 52 cases, by amniocentesis in 12 while two were diagnosed by analysis of free foetal DNA obtained from maternal peripheral blood. In 35 (53%) pregnancies the foetus was female. For 31 men (47%), haemophilia status was determined by analysis of previously determined informative markers or familial mutations (12 affected and 19 unaffected). There may be more than one laboratory involved in the PND diagnostic pathway (providing DNA extraction, karyotype analysis, gender determination, maternal contamination detection, molecular diagnosis and sequencing). Good communication between all the parties, coordinated by the haemophilia centre, is essential for a successful and rapid process.

FⅨ gene all exons sequencing technology in hemophilia B gene carriers detection and the application of prenatal gene diagnosis

To establish a feasible protocol to provide genetic diagnosis and prenatal diagnosis in Chinese hemophilia patients and their relatives by direct exon sequencing. In our study, genetic diagnosis was performed on 5 unrelated families with informed consent, which included 3 pregnant women who asked for prenatal diagnosis. Umbilical cord blood was obtained from 2 fetuses and amniotic fluid from another fetus. After extraction of the genomic DNA, all of the exons, exon-intron boundaries and their flanks of FⅨ gene were amplified by polymerase chain reaction (PCR). PCR products were detected through direct-sequencing. Sequence analysis indicated that the patients and carriers from 5 families have the pathogenic mutations,c.1022G>A (p.R341Q), c.484 C>T (p. R162X), c.1135C>T (p.R379X), c.799C>T (p.H267Y), c.1232G＞T (p.S411I), respectively. Except c.484 C>T (p. R162X), 4 of the 5 mutations were reported firstly in Chinese population. During prenatal diagnosis, one of the fetuses was found to be affected with c.484C>T; p.R162X. The remaining two fetuses were diagnosed as normal, the results of which were later verified by post-birth diagnosis, and factor FⅨ activities in plasma was 52.7% and 76.2%, respectively. In the quest of strict quality control, exon sequence on FⅨ gene was a rapid and accurate method for genetic diagnosis and prenatal diagnosis of hemophilia B.

Prevalence of Intron 1 Inversion of Cases With Hemophilia A in North Indian Population

Hemophilia A is an X-linked bleeding disorder resulting from heterogeneous mutations in the factor VIII (FVIII) gene. The disease is frequently caused by intron 22 inversion mutation in FVIII gene in approximately 50% cases and by intron 1 inversion (Inv1) in 2% to 5% cases with severe hemophilia A. Both inversion mutations occur due to intrachromosomal recombination between inverted repeats found in intronic sequences in upstream regions located telomeric to the FVIII gene and result in a severe phenotype. Frequency of Inv1 mutation varies in different populations. We have analyzed the frequency of the Inv1 in a group of 110 cases with Hemophilia A from North Indian Population and found 4 inversion-positive cases (3.6%). The Inv1 genotyping was further applied to analyze the hemophilia carrier status of the mother and proband's sister. Direct mutation detection strategy is more perfective in diagnosis of cases, carriers, and in prenatal diagnosis of hemophilia A.

Combined analysis of the MspI and XbaI polymorphisms in intron 22 of the factor VIII gene for detection of hemophilia A in a Korean population

To determine the usefulness of MspI/int22h-1 (intron 22 homologous region-1) polymorphism of the factor VIII gene for molecular genetic diagnosis of hemophilia A in the Korean population, MspI/intron 22 and XbaI/intron 22 polymorphisms were analyzed in 101 unrelated Korean families with severe hemophilia A. The expected heterozygosity rates of MspI/int22h-1 and XbaI/int22h-1 polymorphisms were 49.5 and 43.6%, respectively; these polymorphisms were not in complete linkage disequilibrium. Combined analysis using both polymorphisms provided an informative rate of 66.3%. These results suggest that PCR analysis of the MspI/int22h-1 polymorphism of the factor VIII gene would be useful for carrier detection and prenatal diagnosis of hemophilia A in the Korean population.

The status of carrier and prenatal diagnosis of haemophilia in China

Haemophilia A (HA) and haemophilia B (HB) are the most common X-linked inherited bleeding disorders. It is important to detect the carrier women in families with HA/HB and subsequent antenatal diagnosis of confirmed carriers. This study consists of 102 HA families which include 68 mothers for prenatal diagnosis and 107 female relatives for carrier diagnosis, and 29 HB families which include 16 mothers and 31 female relatives respectively. The rapid fluorescent PCR with two groups of different combined polymorphism markers was applied for linkage analysis in HA and HB families respectively. The Amelogenin gene was added to help the detection of gender diagnosis. Gene sequencing was also used to detect the mutations directly. There were 37 causative F8C mutations (23 novel) and 24 causative F9C mutations (eight novel) found in this cohort of patients. Few of the women could not be diagnosed due to homologous recombination and/or inability to locate the mutation. Complicated cases have been found in some families. With regard to carrier and prenatal diagnosis, it was considered that genetic diagnosis by linkage analysis and direct sequencing was successful. Some special families might require combination of the linkage analysis and gene sequence for a successful diagnosis. New intragenic SNP and STR sites special to Chinese population need to be discovered.

Prenatal diagnosis strategy of hemophilia A with different clinical backgrounds

Objective To prenatally diagnose HA fetus with different clinical backgrounds. Methods Genetic tests were performed on 15 gravidas subjected for prenatal diagnosis of HA and different methods were employed for diagnosis according to the gestational weeks and clinical data. Amniotic fluid were taken from pregnant women within 23 gestational weeks for direct genotyping and indirect linkage analysis, since these women had probands with clear-cut mutations. Cordocentesis was performed for linkage analysis in pregnant women over 23 gestational weeks with probands whose types of mutation were unknown, while the FⅧ activity tests were carried out simultaneously. For the pregnant women over 23 gestational weeks without proband, cordocentesis was operated for measurement of FⅧ activity and karyotyping, but carriers of hemophilia A could not be detected in these cases. The introns 22 and 1 inversion of F8 gene were identified by long distance-polymerase chain reaction. Nucleotide sequencing was employed if the gene inversion could not be found and linkage analysis of 7 polymorphic markers, including DXS1108, F8Civs13, INTRON22,DXS1073,DXS9901, DXS15, DXS8069 and sex site (Amelo) were applied eventually. Identification of maternal blood contamination must be done before the tests. Results Fifteen samples were identified without maternal blood contamination. Five fetuses were diagnosed with hemophilia A. Meanwhile there were three pregnant women whose cord blood FⅧ activities were less than 1%. One of them was accompanied by trisomy 21; another had inversion mutation in introns 22 of F8 gene; the remaining one was identified with missense mutation in exon 23 (p. Arg2182Cys) of F8 gene. Conclusions Diverse methods should be applied in prenatal diagnosis of hemophilia A with different clinical backgrounds, for the sake of birth defects prevention. Key words: Hemophilia A; Factor Ⅷ; Prenatal diagnosis

Informativeness of St14 VNTR Polymorphic Marker in the Carrier Detection of Hemophilia A

AbstractHemophilia A is the most common hereditary severe disorder of blood clotting. In families affected with hemophilia, genetic analysis provides opportunities to prevent recurrence of the disease. This study establishes a diagnostic strategy for carrier-ship determination in Pakistani population using an extragenic polymorphic marker for the first time. The analysis of St14 VNTR (DXS52) was carried out by polymerase chain reaction (PCR), in order to determine its informativeness in terms of heterozygosity in Pakistani population. This may be a milestone for further analysis of other polymorphic markers for carrier detection and prenatal diagnosis of hemophilia. Seventy eight blood samples (Hemophiliac = 23, Normal = 55) from 15 families were analyzed for determining informativeness of St14 VNTR in carrier detection of hemophilia A. A total of nine alleles (2400, 2100, 1750, 1690, 1630, 1570, 1390, 1300, 1220 bp) was detected in the pool of subjects. 19 out of 40 females were found to be carriers with respect to the St14 VNTR polymorphic marker. The marker was informative in 73.33% of families. The expected heterozygosity rate of the St14 VNTR was 0.86 while the observed heterozygosity was 0.7. This shows that St14 VNTR is 70% informative in our population, allowing it to be a useful marker in carrier detection, as informativeness is the direct reflection of heterozygosity of a polymorphic marker.

Informativeness of St14 VNTR Polymorphic Marker in the Carrier Detection of Hemophilia A

Hemophilia A is the most common hereditary severe disorder of blood clotting. In families affected with hemophilia, genetic analysis provides opportunities to prevent recurrence of the disease. This study establishes a diagnostic strategy for carrier-ship determination in Pakistani population using an extragenic polymorphic marker for the first time. The analysis of St14 VNTR (DXS52) was carried out by polymerase chain reaction (PCR), in order to determine its informativeness in terms of heterozygosity in Pakistani population. This may be a milestone for further analysis of other polymorphic markers for carrier detection and prenatal diagnosis of hemophilia. Seventy eight blood samples (Hemophiliac = 23, Normal = 55) from 15 families were analyzed for determining informativeness of St14 VNTR in carrier detection of hemophilia A. A total of nine alleles (2400, 2100, 1750, 1690, 1630, 1570, 1390, 1300, 1220 bp) was detected in the pool of subjects. 19 out of 40 females were found to be carriers with respect to the St14 VNTR polymorphic marker. The marker was informative in 73.33% of families. The expected heterozygosity rate of the St14 VNTR was 0.86 while the observed heterozygosity was 0.7. This shows that St14 VNTR is 70% informative in our population, allowing it to be a useful marker in carrier detection, as informativeness is the direct reflection of heterozygosity of a polymorphic marker.

O1053 Multiplex fluorescent analysis of four short tandem repeats for prenatal diagnosis of haemophilia A in China

O1053 Multiplex fluorescent analysis of four short tandem repeats for prenatal diagnosis of haemophilia A in China

Detection of factor VIII intron 1 inversion in severe haemophilia A

Screening the intron 1 inversion of factor VIII (FVIII) in the population of severe haemophilia A(HA) in China and performing carrier detection and prenatal diagnosis. Using LD-PCR to detect intron 22 inversions and multiple-PCR within two tubes to intron 1 inversions in severe HA patients. Carrier detection and prenatal diagnosis were performed in affected families. Linkage analysis and DNA sequencing were used to verify these tests. One hundred and eighteen patients were seven diagnosed as intron 22 inversions and 7 were intron 1 inversions out of 247 severe HA patients. The prevalence of the intron 1 inversion in Chinese severe haemophilia A patients was 2.8% (7/247). Six women from family A and 2 from family B were diagnosed as carriers. One fetus from family A was affected fetus. Intron 1 inversion could be detected directly by multiple-PCR within two tubes. This method made the strategy more perfective in carrier and prenatal diagnosis of haemophilia A.

The use of DNA markers for carrier detection and prenatal diagnosis of haemophilia A in Egyptian families

Haemophilia A is the most common inherited X-linked recessive bleeding disorder. The aim was to investigate the usefulness of two DNA markers in linkage analysis, one intragenic BCL1 affecting restriction site in intron 18, and is detected as restriction fragment length polymorphism (RFLP), and one extragenic variable number of tandem repeat (VNTR) locus DXS52 (St14) to formulate an informative and accurate carrier detection and prenatal diagnosis. The study included 46 families with at least one child affected with haemophilia A, and 30 unrelated normal females as control group. Polymerase chain reaction (PCR) and restriction enzyme analysis were used to study the polymorphism in BCL1, and long-distance PCR for detection of VNTR (ST14) alleles. The incidence of BCL1 (+) allele was 74%, 72% and 60% in patients, mothers and control group, respectively. Expected heterozygosity for BCL1 was 40% in mothers of affected cases compared with 48% in the female control group. However, observed heterozygosity was found to be 48% in the mothers of affected cases, compared with 60% in the control group. Thus, 48% of the studied families are informative for this marker alone. Nine different alleles of VNTR (St14) were observed in mothers and six alleles in affected cases and six in the control group. The most prevalent alleles were 1300 bp (45.5% and 34%) and 700 bp (13.6% and 20%) in patients and their mothers, respectively. Observed heterozygosity in mothers was 41% compared with 43.3% in controls. The combined use of both BCL1 and St14 markers raised the informative rate to 63.6%. Carrier detection and prenatal diagnosis is possible in haemophilia A families using both DNA markers. We suggest screening haemophilic families first for BCL1 polymorphism followed by analysis of St14 locus.

Factor IX gene haplotypes and its relevance for the indirect genetic analysis of haemophilia B in its Indian perspective

In developing countries, especially in those with limited facilities and low budget resources, a reliable approach to carrier detection and prenatal diagnosis of haemophilia B might be based on indirect diagnostic strategies. As, the cost-effectiveness of indirect genetic analysis of haemophilia B has been little investigated so far, we here report our experience in India. Polymerase chain reaction analysis of DdeI/intron1, XmnI/intron 3 and HhaI/3' flanking region of the gene for factor IX (F9) was investigated in 68 individuals (23 haemophilia patients, 18 obligate carriers, 27 probable carriers) from 23 families of haemophilia B. Linkage disequilibrium analysis was done and haplotypes were generated employing the expectation-maximization algorithm. DdeI (+) and (-) allele frequencies were found to be 0.522 and 0.478, respectively, with the highest observed heterozygosity of 46.6% as compared to XmnI (24.4%) and HhaI (42.2%). The frequencies of haplotype III and VI, that is DdeI (+)-XmnI (-)-HhaI (-) and DdeI (-)-XmnI (-)-HhaI (-) were observed to be 0.363 and 0.257, respectively. Haplotype III was found to be the most heterogeneous that suggests its efficacy in the indirect genetic analysis of F9 gene. Linkage disequilibrium analysis revealed no association between DdeI/HhaI (D' = 0.092); however, significant but incomplete linkage disequilibrium was observed in XmnI/HhaI and DdeI/XmnI (D' = 0709, 0.515, respectively). The overall cumulative polymorphism information content of these three markers increased from about 0.33 to 0.72, which suggested the efficiency of haplotyping of these markers over individual gene analysis in the direction of carrier assessment of haemophilia B in India.

Population and molecular-genetic aspects of Haemophilia A and Haemophilia B in Uzbekistan

The present study summarizes results of retrospective epidemiological and molecular-genetic investigations of Haemophilia A and Haemophilia B in Uzbekistan. In the period from 1991 to 2004, a combined total of 1304 cases of Haemophilia A and Haemophilia B were recorded in the republic. The morbidity index varied from 0.75 to 1.46 per 10000 newborn male infants. The mean birth rate of patients with Haemophilia A and Haemophilia B amounted to 1: 8735 (1.14 × 10−4) of newborn male infants. Features of certain DNA-polymorphisms in the genes of blood coagulation factors VIII and IX in the Uzbek population were analyzed. The frequencies of alleles were studied and the information value of these genetic markers for ascertaining genetic carriage and prenatal diagnosis of Haemophilia A and Haemophilia B was determined. Results of DNA diagnosis of Haemophilia A and Haemophilia B are summarized.

Evolution of Prenatal Diagnostic Techniques From Phenotypic Diagnosis to Gene Arrays: Its Likely Impact on Prenatal Diagnosis of Hemophilia

Prenatal diagnostic techniques in hemophilia have evolved through the early sex-determination techniques of offering a nonspecific diagnosis in case of a male fetus through the various mutation screening techniques to the more recent gene array techniques. Each of these techniques has specific advantages and disadvantages. The sampling techniques have evolved simultaneously to suit the requirements of each technique and also the different gestation periods. The DNA-based testing methods provide a range of aberrations detected with different levels of genomic resolution. The more recent gene array analysis is poised to have substantial impact on prenatal diagnosis of hemophilia not only in studying the highly heterogeneous mutations but may also be useful in studying the effect of various ameliorating or epistatic genetic mutations/ polymorphisms simultaneously, providing a wide range of options to the prenatal diagnosis experts, the genetic counselors, and the couples opting for prenatal diagnosis.