Noninvasive prenatal diagnosis of hemophilia by microfluidics digital PCR analysis of maternal plasma DNA. 2011

Nancy B Y Tsui, and Rezan A Kadir, and K C Allen Chan, and Claudia Chi, and Gillian Mellars, and Edward G Tuddenham, and Tak Y Leung, and Tze K Lau, and Rossa W K Chiu, and Y M Dennis Lo
Centre for Research into Circulating Fetal Nucleic Acids, Li Ka Shing Institute of Health Sciences, Hong Kong, China.

Hemophilia is a bleeding disorder with X-linked inheritance. Current prenatal diagnostic methods for hemophilia are invasive and pose a risk to the fetus. Cell-free fetal DNA analysis in maternal plasma provides a noninvasive mean of assessing fetal sex in such pregnancies. However, the disease status of male fetuses remains unknown if mutation-specific confirmatory analysis is not performed. Here we have developed a noninvasive test to diagnose whether the fetus has inherited a causative mutation for hemophilia from its mother. The strategy is based on a relative mutation dosage approach, which we have previously established for determining the mutational status of fetuses for autosomal disease mutations. In this study, the relative mutation dosage method is used to deduce whether a fetus has inherited a hemophilia mutation on chromosome X by detecting whether the concentration of the mutant or wild-type allele is overrepresented in the plasma of heterozygous women carrying male fetuses. We correctly detected fetal genotypes for hemophilia mutations in all of the 12 studied maternal plasma samples obtained from at-risk pregnancies from as early as the 11th week of gestation. This development would make the decision to undertake prenatal testing less traumatic and safer for at-risk families.

UI MeSH Term Description Entries
D008297 Male Males
D009035 Mothers Female parents, human or animal. Mothers' Clubs,Club, Mothers',Clubs, Mothers',Mother,Mother Clubs,Mother's Clubs,Mothers Clubs,Mothers' Club
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D011296 Prenatal Diagnosis Determination of the nature of a pathological condition or disease in the postimplantation EMBRYO; FETUS; or pregnant female before birth. Diagnosis, Prenatal,Fetal Diagnosis,Fetal Imaging,Fetal Screening,Intrauterine Diagnosis,Antenatal Diagnosis,Antenatal Screening,Diagnosis, Antenatal,Diagnosis, Intrauterine,Prenatal Screening,Antenatal Diagnoses,Antenatal Screenings,Diagnosis, Fetal,Fetal Diagnoses,Fetal Imagings,Fetal Screenings,Imaging, Fetal,Intrauterine Diagnoses,Prenatal Diagnoses,Prenatal Screenings,Screening, Antenatal,Screening, Fetal,Screening, Prenatal
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D005260 Female Females
D005838 Genotype The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS. Genogroup,Genogroups,Genotypes
D005865 Gestational Age The age of the conceptus, beginning from the time of FERTILIZATION. In clinical obstetrics, the gestational age is often estimated from the onset of the last MENSTRUATION which is about 2 weeks before OVULATION and fertilization. It is also estimated to begin from fertilization, estrus, coitus, or artificial insemination. Embryologic Age,Fetal Maturity, Chronologic,Chronologic Fetal Maturity,Fetal Age,Maturity, Chronologic Fetal,Age, Embryologic,Age, Fetal,Age, Gestational,Ages, Embryologic,Ages, Fetal,Ages, Gestational,Embryologic Ages,Fetal Ages,Gestational Ages
D006467 Hemophilia A The classic hemophilia resulting from a deficiency of factor VIII. It is an inherited disorder of blood coagulation characterized by a permanent tendency to hemorrhage. Factor VIII Deficiency,Hemophilia,Autosomal Hemophilia A,Classic Hemophilia,Deficiency, Factor VIII,Factor 8 Deficiency, Congenital,Factor VIII Deficiency, Congenital,Haemophilia,Hemophilia A, Congenital,Hemophilia, Classic,As, Autosomal Hemophilia,Autosomal Hemophilia As,Classic Hemophilias,Congenital Hemophilia A,Congenital Hemophilia As,Hemophilia A, Autosomal,Hemophilia As,Hemophilia As, Autosomal,Hemophilia As, Congenital,Hemophilias, Classic
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

Related Publications

Nancy B Y Tsui, and Rezan A Kadir, and K C Allen Chan, and Claudia Chi, and Gillian Mellars, and Edward G Tuddenham, and Tak Y Leung, and Tze K Lau, and Rossa W K Chiu, and Y M Dennis Lo
January 2022, Fetal diagnosis and therapy,
Nancy B Y Tsui, and Rezan A Kadir, and K C Allen Chan, and Claudia Chi, and Gillian Mellars, and Edward G Tuddenham, and Tak Y Leung, and Tze K Lau, and Rossa W K Chiu, and Y M Dennis Lo
January 2006, Methods in molecular biology (Clifton, N.J.),
Nancy B Y Tsui, and Rezan A Kadir, and K C Allen Chan, and Claudia Chi, and Gillian Mellars, and Edward G Tuddenham, and Tak Y Leung, and Tze K Lau, and Rossa W K Chiu, and Y M Dennis Lo
February 2013, Clinical chemistry,
Nancy B Y Tsui, and Rezan A Kadir, and K C Allen Chan, and Claudia Chi, and Gillian Mellars, and Edward G Tuddenham, and Tak Y Leung, and Tze K Lau, and Rossa W K Chiu, and Y M Dennis Lo
June 2012, Expert review of molecular diagnostics,
Nancy B Y Tsui, and Rezan A Kadir, and K C Allen Chan, and Claudia Chi, and Gillian Mellars, and Edward G Tuddenham, and Tak Y Leung, and Tze K Lau, and Rossa W K Chiu, and Y M Dennis Lo
November 2013, Clinical chemistry,
Nancy B Y Tsui, and Rezan A Kadir, and K C Allen Chan, and Claudia Chi, and Gillian Mellars, and Edward G Tuddenham, and Tak Y Leung, and Tze K Lau, and Rossa W K Chiu, and Y M Dennis Lo
August 2012, The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians,
Nancy B Y Tsui, and Rezan A Kadir, and K C Allen Chan, and Claudia Chi, and Gillian Mellars, and Edward G Tuddenham, and Tak Y Leung, and Tze K Lau, and Rossa W K Chiu, and Y M Dennis Lo
January 2004, Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban,
Nancy B Y Tsui, and Rezan A Kadir, and K C Allen Chan, and Claudia Chi, and Gillian Mellars, and Edward G Tuddenham, and Tak Y Leung, and Tze K Lau, and Rossa W K Chiu, and Y M Dennis Lo
January 2002, Expert review of molecular diagnostics,
Nancy B Y Tsui, and Rezan A Kadir, and K C Allen Chan, and Claudia Chi, and Gillian Mellars, and Edward G Tuddenham, and Tak Y Leung, and Tze K Lau, and Rossa W K Chiu, and Y M Dennis Lo
December 2008, Proceedings of the National Academy of Sciences of the United States of America,
Nancy B Y Tsui, and Rezan A Kadir, and K C Allen Chan, and Claudia Chi, and Gillian Mellars, and Edward G Tuddenham, and Tak Y Leung, and Tze K Lau, and Rossa W K Chiu, and Y M Dennis Lo
November 1990, Zhonghua fu chan ke za zhi,
Copied contents to your clipboard!