Detection of fetal HLA‐DQα sequences in maternal blood: A gender‐independent technique of fetal cell identification

Geifman-Holtzman, Ossie; Holtzman, Eliezer J.; Vadnais, Theresa J.; Phillips, Vincent E.; Capeless, Eleanor L.; Bianchi, Diana W.

doi:10.1002/pd.1970150309

Cited by 15 publications

(7 citation statements)

References 21 publications

(24 reference statements)

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“…By doing this, high accuracy was achieved similar to the accuracy of FfDNA from maternal plasma. Additionally, when FfDNA is used, a carefully selected internal positive control to confirm the presence of fetal DNA must be used, either SRY gene in male fetuses or other polymorphic markers in female fetuses, such as HLA gene 29 for when HLA differences exist between both parents. Alternatively, using fetal/maternal methylation differences such as the hypermethylated fetal RASSF1A gene or the hypomethylated Maspin gene that serves as control for the presence of FfDNA as was previously reported.…”

Section: Discussionmentioning

confidence: 99%

Noninvasive fetal RhCE genotyping from maternal blood

Geifman-Holtzman

Grotegut

Gaughan

et al. 2008

BJOG

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Background The successful prevention of RhD disease has brought attention to other red blood cells' antigens causing alloimmunisation including RhC/c and RhE/e. Prenatal diagnosis of fetal Rh genotype from maternal blood is in clinical use in Europe but not in the USA.Objective To estimate the collective reported diagnostic accuracy of fetal RhCE genotyping from peripheral maternal blood and compare the results of genotyping when fetal cells and free fetal DNA (FfDNA) are used.Search strategy English-written literature describing fetal RhCE determination from maternal blood using fetal cells or FfDNA was performed using medical subject headings and text words. The sources included Pubmed (1966Pubmed ( -2007, Ovid , CINAHL, The Cochrane Library, ACP Journal Club and OCLC. Key words were prenatal diagnosis, fetal RhCE, fetal DNA in maternal blood and alloimmunisation.Selection criteria A study was considered eligible if it described fetal RhCE type determination using maternal peripheral blood reported in the English literature. Abstracts were excluded.Data collection and analysis From each study, we determined the number of samples tested, fetal RhCE genotype, the source of the fetal DNA, gestational age, presence of alloimmunisation and confirmation of fetal RhCE type. Exclusions and inclusions were noted. We calculated composite estimates of accuracy using a weighted random effects model. We assessed the papers against an international quality, STARD checklist which is standards for reporting studies of diagnostic accuracy.Main results We identified 20 protocols in six English-written publications reporting fetal RhC/c (seven protocols) and/or E/e (13 protocols) genotyping using DNA obtained from maternal blood for a total of 369 samples. For RhC/c, 176 samples were tested and for RhE/e, 193 samples were tested. Accuracy was determined for each study and for all studies. The combined accuracy of fetal genotype was 96.3% for RhC/c and 98.2% for RhE/e. Only a few samples of the sorted cells were found to be a source for accurate diagnosis, but plasma was consistently the best source of fetal RhCE genotyping in 147/147 (100%) for RhC/c and 168/168 (100%) for RhE/e.Conclusions The combined accuracy of noninvasive fetal RhC/c or RhE/e determination using maternal peripheral blood is 96.3% and 98.2%, respectively. FfDNA in maternal plasma is a better source for genotyping reported to be 100% correct for both RHCE genotypes. Further studies and reports of accuracy from laboratories performing the tests are required before prenatal determination of fetal RhC/c or RhE/e genotypes from maternal blood can safely replace the current methods used in the management of the RhC/c or RhE alloimmunised pregnancies.

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Section: Discussionmentioning

confidence: 99%

Noninvasive fetal RhCE genotyping from maternal blood

Geifman-Holtzman

Grotegut

Gaughan

et al. 2008

BJOG

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“…In the presence of positive end-diastolic flow in the umbilical artery without any associated findings a pulsatility index (PI) [35] above a critical level is associated with increased fetal blood lactate levels [28]. With additional centralization, or the development of late decelerations on the fetal heart rate tracing, significantly lower oxygen content and pH values are associated with a concomitant rise in carbon dioxide and lactate in cord artery blood [14,94,95].…”

Section: The Fetal Circulation In Intrauterine Growth Restrictionmentioning

confidence: 99%

“…Uniquely fetal gene sequences that have been detected by PCR include the Υ chromosome, various beta globin genes, such as hemoglobin Boston-Lepore or mutations associated with jS-thalassemia [1,3,15,33,38,46,67]. The HLA DR and DQ alpha genes have also been detected in fetal cells in maternal blood [28,80]. Non-invasive fetal Rhesus D genotyping in Rhesus D negative pregnant women has potential clinical applications [41,62].…”

Section: Genetic Analysis Of Fetal Cells In Maternal Bloodmentioning

confidence: 99%

“…Over the last decades, it was held that as soon as the blastocyst is embedded in maternal decidua, trophoblasts invade maternal circulation and maternal blood fills the lakes within the intervillous space [28,34]. This was thought to be teleological because it was believed that oxygen rich blood is essential for early embryonic development.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Review articles

Gardosi

1998

Jpme

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Individually adjusted or 'customised' growth charts aim to optimise the assessment of fetal growth by taking individual variation into account, and by projecting an optimal curve which delineates the potential weight gain in each pregnancy. This results in an increased detection rate of true growth restriction and a reduction in false positive diagnoses for IUGR. An adjustable standard can apply across geographical boundaries, as individual variation exceeds that between different maternity populations.

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“…Thus, the development of a suitable method for prenatal diagnosis is required for severe genetic disorders, such as OTC deficiency and Duchenne muscular dystrophy (DMD). Various approaches to the prenatal diagnosis of genetic disorders by using the DNA of fetal cells have been investigated (Sekizawa et al 1996a, b;Cheung et al 1996;Geifman et al 1995;Bianchi et al 1990Bianchi et al , 1994Suzumori et al 1992;Lo et al 1989;Herzenberg et al 1979;Douglas et al 1959). Although prenatal diagnosis based on amniocytes or chorionic villus cells is highly accurate, these procedures are invasive and carry a small, yet definite, risk for the developing fetus (Williamson 1996).…”

Section: Introductionmentioning

confidence: 99%

Prenatal diagnosis of ornithine transcarbamylase deficiency by using a single nucleated erythrocyte from maternal blood

et al. 1998

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We have developed a method that allows the prenatal DNA diagnosis of ornithine transcarbamylase (OTC) deficiency by using a single fetal nucleated erythrocyte (NRBC) isolated from maternal blood. OTC gene analysis of a male patient (TF) with early onset OTC deficiency was performed by single-strand conformation polymorphism (PCR-SSCP) and DNA sequencing. To investigate the possible prenatal diagnosis of OTC deficiency, maternal blood was obtained at 13 weeks of gestation of a subsequent pregnancy, from the mother of patient TF. NRBCs in the maternal blood were separated by using the density gradient method and then collected with a micromanipulator. The entire genome of a single NRBC was amplified by primer extension preamplification (PEP). The human leukocyte antigen (HLA)-DQ alpha genotype and sex were determined from small aliquots of the PEP product. The HLA-DQ alpha genotype of each of the parents of the male patient was also determined. Once a single NRBC had been identified as being of fetal origin, the OTC gene was analyzed by using the restriction fragment length polymorphism (RFLP) method. DNA analysis revealed a point mutation in exon 9 of the OTC gene in the OTC-deficient patient (TF). All NRBCs retrieved from maternal blood were successfully identified as being of fetal origin by HLA-DQ alpha genotyping and sex determination. RFLP analysis demonstrated that the fetal OTC gene was normal. This is the first study to successfully diagnose OTC deficiency prenatally, by using a single fetal NRBC from the maternal circulation. Such prenatal DNA diagnosis is non-invasive and can be applied to other genetic diseases, including autosomal and X-linked diseases.

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Detection of fetal HLA‐DQα sequences in maternal blood: A gender‐independent technique of fetal cell identification

Cited by 15 publications

References 21 publications

Noninvasive fetal RhCE genotyping from maternal blood

Noninvasive fetal RhCE genotyping from maternal blood

Review articles

Prenatal diagnosis of ornithine transcarbamylase deficiency by using a single nucleated erythrocyte from maternal blood

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