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Am J Perinatol 2007; 24(3): 167-181
DOI: 10.1055/s-2007-972927
Copyright © 2007 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Proteomics: A Novel Methodology to Complement Prenatal Diagnosis of Chromosomal Abnormalities and Inherited Human Diseases

Mert Ozan Bahtiyar1 , Joshua A. Copel1 , Maurice J. Mahoney1 , 2 , Irina A. Buhimschi1 , Catalin S. Buhimschi1
  • 1Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut
  • 2Department of Genetics, Yale University School of Medicine, New Haven, Connecticut
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Publication History

Publication Date:
19 March 2007 (online)

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ABSTRACT

The current revolution in biomedical sciences has raised new hope for early diagnosis, prevention, and treatment of human diseases. Recent advancements in genomics, proteomics, and other basic sciences are currently transforming the medical science, and offer the promise of answering many of the questions related to human diseases, including their early and accurate diagnosis. Profiling of biological fluids (i.e., serum, urine, amniotic fluid, and cerebrospinal fluid) has successfully identified relevant protein biomarkers that potentially can change early diagnosis and treatment of several medical conditions related to human pregnancy. Similarly, proteomics holds the promise to complement genomics to revolutionize screening and prenatal diagnosis of genetic conditions during early pregnancy. This article summarizes current technology and reviews the application of proteomics in diagnosis of genetic disorders during human pregnancy.

KEYWORDS

Prenatal - diagnosis - proteomics - amniotic fluid

REFERENCES

  • 1 Adams M M, Erickson J D, Layde P M, Oakley G P. Down's syndrome: recent trends in the United States.  JAMA. 1981;  246 758-760
    CrossrefPubMedGoogle Scholar
  • 2 Egan J F, Kaminsky L M, DeRoche M E, Barsoom M J, Borgida A F, Benn P A. Antenatal Down syndrome screening in the United States in 2001: a survey of maternal-fetal medicine specialists.  Am J Obstet Gynecol. 2002;  187 1230-1234
    CrossrefPubMedGoogle Scholar
  • 3 Akesson H O, Forssman H. A study of maternal age in Down's syndrome.  Ann Hum Genet. 1966;  29 271-276
    PubMedGoogle Scholar
  • 4 Brock D J, Sutcliffe R G. Alpha-fetoprotein in the antenatal diagnosis of anencephaly and spina bifida.  Lancet. 1972;  2 197-199
    PubMedGoogle Scholar
  • 5 Palomaki G E, Knight G J, McCarthy J, Haddow J E, Eckfeldt J H. Maternal serum screening for fetal Down syndrome in the United States: a 1992 survey.  Am J Obstet Gynecol. 1993;  169 1558-1562
    PubMedGoogle Scholar
  • 6 Haddow J E, Palomaki G E, Knight G J, Cunningham G C, Lustig L S, Boyd P A. Reducing the need for amniocentesis in women 35 years of age or older with serum markers for screening.  N Engl J Med. 1994;  330 1114-1118
    CrossrefPubMedGoogle Scholar
  • 7 Haddow J E, Palomaki G E, Knight G J, Foster D L, Neveux L M. Second trimester screening for Down's syndrome using maternal serum dimeric inhibin A.  J Med Screen. 1998;  5 115-119
    PubMedGoogle Scholar
  • 8 Canick J A, Palomaki G E, Osathanondh R. Prenatal screening for trisomy 18 in the second trimester.  Prenat Diagn. 1990;  10 546-548
    PubMedGoogle Scholar
  • 9 Saller Jr D N, Canick J A, Blitzer M G et al.. Second-trimester maternal serum analyte levels associated with fetal trisomy 13.  Prenat Diagn. 1999;  19 813-816
    CrossrefPubMedGoogle Scholar
  • 10 Williamson R A, Weiner C P, Patil S, Benda J, Varner M W, Abu-Yousef M M. Abnormal pregnancy sonogram: selective indication for fetal karyotype.  Obstet Gynecol. 1987;  69 15-20
    PubMedGoogle Scholar
  • 11 Bahado-Singh R O, Deren O, Tan A et al.. Ultrasonographically adjusted midtrimester risk of trisomy 21 and significant chromosomal defects in advanced maternal age.  Am J Obstet Gynecol. 1996;  175 1563-1568
    CrossrefPubMedGoogle Scholar
  • 12 Goldstein I, Gomez K, Copel J A. Fifth digit measurement in normal pregnancies: a potential sonographic sign of Down's syndrome.  Ultrasound Obstet Gynecol. 1995;  5 34-37
    PubMedGoogle Scholar
  • 13 Lockwood C J, Lynch L, Berkowitz R L. Ultrasonographic screening for the Down syndrome fetus.  Am J Obstet Gynecol. 1991;  165 349-352
    PubMedGoogle Scholar
  • 14 American College of Obstetricians and Gynecologists Committee on Practice Bulletins-Obstetrics . ACOG practice bulletin. Clinical management guidelines for obstetrician-gynecologists. Prenatal diagnosis of fetal chromosomal abnormalities.  Obstet Gynecol. 2001;  97(suppl) 1-12
    CrossrefPubMedGoogle Scholar
  • 15 Nicolaides K H, Azar G, Byrne D, Mansur C, Marks K. Fetal nuchal translucency: ultrasound screening for chromosomal defects in first trimester of pregnancy.  BMJ. 1992;  304 867-869
    PubMedGoogle Scholar
  • 16 Haddow J E, Palomaki G E, Knight G J, Williams J, Miller W A, Johnson A. Screening of maternal serum for fetal Down's syndrome in the first trimester.  N Engl J Med. 1998;  338 955-961
    CrossrefPubMedGoogle Scholar
  • 17 Krantz D A, Larsen J W, Buchanan P D, Macri J N. First-trimester Down syndrome screening: free beta-human chorionic gonadotropin and pregnancy-associated plasma protein A.  Am J Obstet Gynecol. 1996;  174 612-616
    CrossrefPubMedGoogle Scholar
  • 18 Snijders R J, Noble P, Sebire N, Souka A, Nicolaides K H. UK multicentre project on assessment of risk of trisomy 21 by maternal age and fetal nuchal-translucency thickness at 10-14 weeks of gestation. Fetal Medicine Foundation First Trimester Screening Group.  Lancet. 1998;  352 343-346
    CrossrefPubMedGoogle Scholar
  • 19 Wapner R, Thom E, Simpson J L et al.. First Trimester Maternal Serum Biochemistry and Fetal Nuchal Translucency Screening (BUN) Study Group . First-trimester screening for trisomies 21 and 18.  N Engl J Med. 2003;  349 1405-1413
    CrossrefPubMedGoogle Scholar
  • 20 Papageorghiou A T, Avgidou K, Spencer K, Nix B, Nicolaides K H. Sonographic screening for trisomy 13 at 11 to 13( + 6) weeks of gestation.  Am J Obstet Gynecol. 2006;  194 397-401
    CrossrefPubMedGoogle Scholar
  • 21 Shimizu C, Bryant-Greenwood P. Post-genome molecular diagnostics in obstetrics.  Curr Opin Obstet Gynecol. 2004;  16 167-177
    PubMedGoogle Scholar
  • 22 Leonard J V, Morris A A. Diagnosis and early management of inborn errors of metabolism presenting around the time of birth.  Acta Paediatr. 2006;  95 6-14
    PubMedGoogle Scholar
  • 23 American College of Obstetrics and Gynecology . ACOG technology assessment. Genetics and molecular diagnostic testing. Number 1, July 2002. American College of Obstetrics and Gynecology.  Int J Gynaecol Obstet. 2002;  79 67-85
    PubMedGoogle Scholar
  • 24 Chiu R W, Lau T K, Cheung P T, Gong Z Q, Leung T N, Lo Y M. Noninvasive prenatal exclusion of congenital adrenal hyperplasia by maternal plasma analysis: a feasibility study.  Clin Chem. 2002;  48 778-780
    PubMedGoogle Scholar
  • 25 Saito H, Sekizawa A, Morimoto T, Suzuki M, Yanaihara T. Prenatal DNA diagnosis of a single-gene disorder from maternal plasma.  Lancet. 2000;  356 1170
    CrossrefPubMedGoogle Scholar
  • 26 Watanabe A, Sekizawa A, Taguchi A et al.. Prenatal diagnosis of ornithine transcarbamylase deficiency by using a single nucleated erythrocyte from maternal blood.  Hum Genet. 1998;  102 611-615
    PubMedGoogle Scholar
  • 27 Liu J, Lissens W, Devroey P, Liebaers I, Van Steirteghem A. Cystic fibrosis, Duchenne muscular dystrophy and preimplantation genetic diagnosis.  Hum Reprod Update. 1996;  2 531-539
    CrossrefPubMedGoogle Scholar
  • 28 Bianchi D W. Circulating fetal DNA: its origin and diagnostic potential-a review.  Placenta. 2004;  25(suppl A) S93-S101
    CrossrefPubMedGoogle Scholar
  • 29 Sekizawa A, Saito H. Prenatal screening of single-gene disorders from maternal blood.  Am J Pharmacogenomics. 2001;  1 111-117
    CrossrefPubMedGoogle Scholar
  • 30 Banks R, Selby P. Clinical proteomics: insights into pathologies and benefits for patients.  Lancet. 2003;  362 415-416
    CrossrefPubMedGoogle Scholar
  • 31 Eisenberg B, Wapner R J. Clinical procedures in prenatal diagnosis.  Best Pract Res Clin Obstet Gynaecol. 2002;  16 611-627
    CrossrefPubMedGoogle Scholar
  • 32 Caughey A B, Hopkins L M, Norton M E. Chorionic villus sampling compared with amniocentesis and the difference in the rate of pregnancy loss.  Obstet Gynecol. 2006;  108 612-616
    CrossrefPubMedGoogle Scholar
  • 33 Leschot N J, Verjaal M, Treffers P E. Risks of midtrimester amniocentesis: assessment in 3000 pregnancies.  Br J Obstet Gynaecol. 1985;  92 804-807
    PubMedGoogle Scholar
  • 34 Nicolaides K, Brizot Mde L, Patel F, Snijders R. Comparison of chorionic villus sampling and amniocentesis for fetal karyotyping at 10-13 weeks' gestation.  Lancet. 1994;  344 435-439
    CrossrefPubMedGoogle Scholar
  • 35 Ghidini A, Sepulveda W, Lockwood C J, Romero R. Complications of fetal blood sampling.  Am J Obstet Gynecol. 1993;  168 1339-1344
    PubMedGoogle Scholar
  • 36 Liou J D, Chu D C, Cheng P J et al.. Human chromosome 21-specific DNA markers are useful in prenatal detection of Down syndrome.  Ann Clin Lab Sci. 2004;  34 319-323
    PubMedGoogle Scholar
  • 37 Sanchez-Garcia J F, Gallardo D, Ramirez L, Vidal F. Multiplex fluorescent analysis of four short tandem repeats for rapid haemophilia A molecular diagnosis.  Thromb Haemost. 2005;  94 1099-1103
    PubMedGoogle Scholar
  • 38 Gonzalez-Gonzalez M C, Trujillo M J, Rodriguez de Alba M, Ramos C. Early Huntington disease prenatal diagnosis by maternal semiquantitative fluorescent-PCR.  Neurology. 2003;  60 1214-1215
    PubMedGoogle Scholar
  • 39 Aoshima T, Kajita M, Sekido Y et al.. Carbamoyl phosphate synthetase I deficiency: molecular genetic findings and prenatal diagnosis.  Prenat Diagn. 2001;  21 634-637
    CrossrefPubMedGoogle Scholar
  • 40 Sermon K, Van Steirteghem A, Liebaers I. Preimplantation genetic diagnosis.  Lancet. 2004;  363 1633-1641
    CrossrefPubMedGoogle Scholar
  • 41 Hulten M A, Dhanjal S, Pertl B. Rapid and simple prenatal diagnosis of common chromosome disorders: advantages and disadvantages of the molecular methods FISH and QF-PCR.  Reproduction. 2003;  126 279-297
    CrossrefPubMedGoogle Scholar
  • 42 Verlinsky Y, Ginsberg N, Chmura M et al.. Cross-hybridization of the chromosome 13/21 alpha satellite DNA probe to chromosome 22 in the prenatal screening of common chromosomal aneuploidies by FISH.  Prenat Diagn. 1995;  15 831-834
    CrossrefPubMedGoogle Scholar
  • 43 Wells D, Escudero T, Levy B, Hirschhorn K, Delhanty J D, Munne S. First clinical application of comparative genomic hybridization and polar body testing for preimplantation genetic diagnosis of aneuploidy.  Fertil Steril. 2002;  78 543-549
    CrossrefPubMedGoogle Scholar
  • 44 Surbek D V, Holzgreve W, Nicolaides K H. Haematopoietic stem cell transplantation and gene therapy in the fetus: ready for clinical use?.  Hum Reprod Update. 2001;  7 85-91
    CrossrefPubMedGoogle Scholar
  • 45 Waddington S N, Kramer M G, Hernandez-Alcoceba R et al.. In utero gene therapy: current challenges and perspectives.  Mol Ther. 2005;  11 661-676
    CrossrefPubMedGoogle Scholar
  • 46 Lieber C D. Introduction to proteomics. In: Tools for the New Biology. Totowa, NJ; Humana Press Inc 2002
    Google Scholar
  • 47 Venter J C, Adams M D, Myers E W et al.. The sequence of the human genome.  Science. 2001;  291 1304-1351
    CrossrefPubMedGoogle Scholar
  • 48 Banks R E, Dunn M J, Hochstrasser D F et al.. Proteomics: new perspectives, new biomedical opportunities.  Lancet. 2000;  356 1749-1756
    CrossrefPubMedGoogle Scholar
  • 49 Zenclussen A C, Zenclussen M L, Ritter T, Volk H D. The use of gene therapy tools in reproductive immunology research.  Curr Gene Ther. 2005;  5 459-466
    CrossrefPubMedGoogle Scholar
  • 50 Muthusamy B, Hanumanthu G, Suresh S et al.. Plasma Proteome Database as a resource for proteomics research.  Proteomics. 2005;  5 3531-3536
    CrossrefPubMedGoogle Scholar
  • 51 Monti M, Orru S, Pagnozzi D, Pucci P. Interaction proteomics.  Biosci Rep. 2005;  25 45-56
    CrossrefPubMedGoogle Scholar
  • 52 Mizejewski G J. Biological roles of alpha-fetoprotein during pregnancy and perinatal development.  Exp Biol Med (Maywood). 2004;  229 439-463
    PubMedGoogle Scholar
  • 53 Farag K, Hassan I, Ledger W L. Prediction of preeclampsia: can it be achieved?.  Obstet Gynecol Surv. 2004;  59 464-482
    CrossrefPubMedGoogle Scholar
  • 54 Park K H, Yoon B H, Shim S S, Jun J K, Syn H C. AF tumor necrosis factor-alpha is a marker for the prediction of early-onset neonatal sepsis in preterm labor.  Gynecol Obstet Invest. 2004;  58 84-90
    CrossrefPubMedGoogle Scholar
  • 55 Lockwood C J, Krikun G, Schatz F. Decidual cell-expressed tissue factor maintains hemostasis in human endometrium.  Ann NY Acad Sci. 2001;  943 77-88
    PubMedGoogle Scholar
  • 56 Anderson L, Seilhamer J. A comparison of selected mRNA and protein abundances in human liver.  Electrophoresis. 1997;  18 533-537
    CrossrefPubMedGoogle Scholar
  • 57 Kong F, Nicole White C, Xiao X et al.. Using proteomic approaches to identify new biomarkers for detection and monitoring of ovarian cancer.  Gynecol Oncol. 2006;  100 247-253
    CrossrefPubMedGoogle Scholar
  • 58 Papadopoulos M C, Abel P M, Agranoff D et al.. A novel and accurate diagnostic test for human African trypanosomiasis.  Lancet. 2004;  363 1358-1363
    CrossrefPubMedGoogle Scholar
  • 59 Pucci-Minafra I, Fontana S, Cancemi P, Alaimo G, Minafra S. Proteomic patterns of cultured breast cancer cells and epithelial mammary cells.  Ann NY Acad Sci. 2002;  963 122-139
    PubMedGoogle Scholar
  • 60 Meehan K L, Holland J W, Dawkins H J. Proteomic analysis of normal and malignant prostate tissue to identify novel proteins lost in cancer.  Prostate. 2002;  50 54-63
    CrossrefPubMedGoogle Scholar
  • 61 Buhimschi I A, Christner R, Buhimschi C S. Proteomic biomarker analysis of AF for identification of intra-amniotic inflammation.  BJOG. 2005;  112 173-181
    PubMedGoogle Scholar
  • 62 Buhimschi C S, Bhandari V, Hamar B D et al.. Proteomic profiling of the amniotic fluid to detect inflammation, infection and neonatal sepsis.  PLoS Med. 2007;  4 e18
    CrossrefPubMedGoogle Scholar
  • 63 Buhimschi I A, Buhimschi C S, Weiner C P et al.. Proteomic but not enzyme-linked immunosorbent assay technology detects AF monomeric calgranulins from their complexed calprotectin form.  Clin Diagn Lab Immunol. 2005;  12 837-844
    CrossrefPubMedGoogle Scholar
  • 64 Wang T H, Chang Y L, Peng H H et al.. Rapid detection of fetal aneuploidy using proteomics approaches on AF supernatant.  Prenat Diagn. 2005;  25 559-566
    CrossrefPubMedGoogle Scholar
  • 65 Wiederkehr F, Vonderschmitt D J. [2-dimensional electrophoresis of cerebrospinal fluid in various neurological patients].  Schweiz Med Wochenschr. 1985;  115 368-373
    PubMedGoogle Scholar
  • 66 Chen J H, Chang Y W, Yao C W et al.. Plasma proteome of severe acute respiratory syndrome analyzed by two-dimensional gel electrophoresis and mass spectrometry.  Proc Natl Acad Sci USA. 2004;  101 17039-17044
    CrossrefPubMedGoogle Scholar
  • 67 Fung K Y, Glode L M, Green S, Duncan M W. A comprehensive characterization of the peptide and protein constituents of human seminal fluid.  Prostate. 2004;  61 171-181
    CrossrefPubMedGoogle Scholar
  • 68 Vuadens F, Benay C, Crettaz D et al.. Identification of biologic markers of the premature rupture of fetal membranes: proteomic approach.  Proteomics. 2003;  3 1521-1525
    CrossrefPubMedGoogle Scholar
  • 69 Unlu M, Morgan M E, Minden J S. Difference gel electrophoresis: a single gel method for detecting changes in protein extracts.  Electrophoresis. 1997;  18 2071-2077
    CrossrefPubMedGoogle Scholar
  • 70 Patterson S D, Aebersold R. Mass spectrometric approaches for the identification of gel-separated proteins.  Electrophoresis. 1995;  16 1791-1814
    CrossrefPubMedGoogle Scholar
  • 71 Gygi S P, Aebersold R. Mass spectrometry and proteomics.  Curr Opin Chem Biol. 2000;  4 489-494
    CrossrefPubMedGoogle Scholar
  • 72 Yates III J R. Mass spectrometry: from genomics to proteomics.  Trends Genet. 2000;  16 5-8
    PubMedGoogle Scholar
  • 73 Kuwata H, Yip T T, Yip C L, Tomita M, Hutchens T W. Bactericidal domain of lactoferrin: detection, quantitation, and characterization of lactoferricin in serum by SELDI affinity mass spectrometry.  Biochem Biophys Res Commun. 1998;  245 764-773
    CrossrefPubMedGoogle Scholar
  • 74 Fung E T, Yip T T, Lomas L et al.. Classification of cancer types by measuring variants of host response proteins using SELDI serum assays.  Int J Cancer. 2005;  115 783-789
    CrossrefPubMedGoogle Scholar
  • 75 Hermjakob H, Apweiler R. The Proteomics Identifications Database (PRIDE) and the ProteomExchange Consortium: making proteomics data accessible.  Expert Rev Proteomics. 2006;  3 1-3
    CrossrefPubMedGoogle Scholar
  • 76 Lo S L, You T, Lin Q, Joshi S B, Chung M C, Hew C L. SPLASH: systematic proteomics laboratory analysis and storage hub.  Proteomics. 2006;  6 1758-1769
    CrossrefPubMedGoogle Scholar
  • 77 Hochstrasser D F. Proteome in perspective.  Clin Chem Lab Med. 1998;  36 825-836
    CrossrefPubMedGoogle Scholar
  • 78 Gross S J, Ferreira J C, Morrow B et al.. Gene expression profile of trisomy 21 placentas: a potential approach for designing noninvasive techniques of prenatal diagnosis.  Am J Obstet Gynecol. 2002;  187 457-462
    CrossrefPubMedGoogle Scholar
  • 79 Oh J E, Fountoulakis M, Juranville J F, Rosner M, Hengstschlager M, Lubec G. Proteomic determination of metabolic enzymes of the amnion cell: basis for a possible diagnostic tool?.  Proteomics. 2004;  4 1145-1158
    CrossrefPubMedGoogle Scholar
  • 80 Hasegawa Y, Iga M, Kimura M, Shigematsu Y, Yamaguchi S. Prenatal diagnosis for organic acid disorders using two mass spectrometric methods, gas chromatography mass spectrometry and tandem mass spectrometry.  J Chromatogr B Analyt Technol Biomed Life Sci. 2005;  823 13-17
    PubMedGoogle Scholar
  • 81 Ramsay S L, Maire I, Bindloss C et al.. Determination of oligosaccharides and glycolipids in AF by electrospray ionisation tandem mass spectrometry: in utero indicators of lysosomal storage diseases.  Mol Genet Metab. 2004;  83 231-238
    CrossrefPubMedGoogle Scholar
  • 82 Yang B Z, Mallory J M, Roe D S et al.. Carnitine/acylcarnitine translocase deficiency (neonatal phenotype): successful prenatal and postmortem diagnosis associated with a novel mutation in a single family.  Mol Genet Metab. 2001;  73 64-70
    CrossrefPubMedGoogle Scholar
  • 83 Busch A, Michel S, Hoppe C, Driesch D, Claussen U, von Eggeling F. Proteome analysis of maternal serum samples for trisomy 21 pregnancies using ProteinChip arrays and bioinformatics.  J Histochem Cytochem. 2005;  53 341-343
    CrossrefPubMedGoogle Scholar
  • 84 Bahtiyar M, Mahoney M, Copel J A. Amniotic fluid proteomic analysis identifies fetal gender and Down syndrome: a new rapid technique for prenatal diagnosis.  Am J Obstet Gynecol. 2002;  187 S181
    PubMedGoogle Scholar
  • 85 D'Alton M, Luthy D, Malone F et al.. Detection of Down syndrome by proteomic profiling of maternal serum.  Am J Obstet Gynecol. 2004;  191 S2
    PubMedGoogle Scholar
  • 86 Vuadens F, Benay C, Crettaz D et al.. Identification of biologic markers of the premature rupture of fetal membranes: proteomic approach.  Proteomics. 2003;  3 1521-1525
    CrossrefPubMedGoogle Scholar
  • 87 Gravett M G, Novy M J, Rosenfeld R G et al.. Diagnosis of intra-amniotic infection by proteomic profiling and identification of novel biomarkers.  JAMA. 2004;  292 462-469
    CrossrefPubMedGoogle Scholar
  • 88 Weiner C P, Lee K Y, Buhimschi C S, Christner R, Buhimschi I A. Proteomic biomarkers that predict the clinical success of rescue cerclage.  Am J Obstet Gynecol. 2005;  192 710-718
    CrossrefPubMedGoogle Scholar
  • 89 Buhimschi C S, Weiner C P, Buhimschi I A. Proteomics, part II: the emerging role of proteomics over genomics in spontaneous preterm labor/birth.  Obstet Gynecol Surv. 2006;  61 543-553
    CrossrefPubMedGoogle Scholar
  • 90 Xiong M, Fang X, Zhao J. Biomarker identification by feature wrappers.  Genome Res. 2001;  11 1878-1887
    PubMedGoogle Scholar
  • 91 Tsangaris G T, Karamessinis P, Kolialexi A et al.. Proteomic analysis of amniotic fluid in pregnancies with Down syndrome.  Proteomics. 2006;  6 4410-4419
    CrossrefPubMedGoogle Scholar
  • 92 Tsui N B, Chiu R W, Ding C et al.. Detection of Trisomy 21 by quantitative mass spectrometric analysis of single-nucleotide polymorphisms.  Clin Chem. 2005;  51 2358-2362
    CrossrefPubMedGoogle Scholar
  • 93 Rinaldo P, Hahn S, Matern D. Clinical biochemical genetics in the twenty-first century.  Acta Paediatr Suppl. 2004;  93 22-26
    PubMedGoogle Scholar
  • 94 Schwab K O, Ensenauer R, Matern D et al.. Complete deficiency of mitochondrial trifunctional protein due to a novel mutation within the beta-subunit of the mitochondrial trifunctional protein gene leads to failure of long-chain fatty acid beta-oxidation with fatal outcome.  Eur J Pediatr. 2003;  162 90-95
    PubMedGoogle Scholar
  • 95 Matern D, He M, Berry S A et al.. Prospective diagnosis of 2-methylbutyryl-CoA dehydrogenase deficiency in the Hmong population by newborn screening using tandem mass spectrometry.  Pediatrics. 2003;  112 74-78
    CrossrefPubMedGoogle Scholar
  • 96 Struys E A, Jansen E E, Gibson K M, Jakobs C. Determination of the GABA analogue succinic semialdehyde in urine and cerebrospinal fluid by dinitrophenylhydrazine derivatization and liquid chromatography-tandem mass spectrometry: application to SSADH deficiency.  J Inherit Metab Dis. 2005;  28 913-920
    CrossrefPubMedGoogle Scholar
  • 97 Thomason M J, Lord J, Bain M D et al.. A systematic review of evidence for the appropriateness of neonatal screening programmes for inborn errors of metabolism.  J Public Health Med. 1998;  20 331-343
    PubMedGoogle Scholar
  • 98 Ho B C, Fenselau C, Hansen G, Larsen J, Daniel A. Dipalmitoylphosphatidylcholine in amniotic fluid quantified by fast-atom-bombardment mass spectrometry.  Clin Chem. 1983;  29 1349-1353
    PubMedGoogle Scholar
  • 99 Jellum E, Kvittingen E A, Stokke O. Mass spectrometry in diagnosis of metabolic disorders.  Biomed Environ Mass Spectrom. 1988;  16 57-62
    CrossrefPubMedGoogle Scholar
  • 100 Shigematsu Y, Kikawa Y, Sudo M, Kanaoka H, Fujioka M, Dan M. Prenatal diagnosis of isovaleric acidemia by fast atom bombardment and tandem mass spectrometry.  Clin Chim Acta. 1991;  203 369-374
    CrossrefPubMedGoogle Scholar
  • 101 Yang B Z, Mallory J M, Roe D S et al.. Carnitine/acylcarnitine translocase deficiency (neonatal phenotype): successful prenatal and postmortem diagnosis associated with a novel mutation in a single family.  Mol Genet Metab. 2001;  73 64-70
    CrossrefPubMedGoogle Scholar
  • 102 Inoue Y, Kuhara T. Rapid and sensitive method for prenatal diagnosis of propionic acidemia using stable isotope dilution gas chromatography-mass spectrometry and urease pretreatment.  J Chromatogr B Analyt Technol Biomed Life Sci. 2002;  776 71-77
    CrossrefPubMedGoogle Scholar
  • 103 Kumps A, Vamos E, Mardens Y, Abramowicz M, Genin J, Duez P. Assessment of an electron-impact GC-MS method for organic acids and glycine conjugates in amniotic fluid.  J Inherit Metab Dis. 2004;  27 567-579
    CrossrefPubMedGoogle Scholar
  • 104 Morel C F, Watkins D, Scott P, Rinaldo P, Rosenblatt D S. Prenatal diagnosis for methylmalonic acidemia and inborn errors of vitamin B12 metabolism and transport.  Mol Genet Metab. 2005;  86 160-171
    CrossrefPubMedGoogle Scholar
  • 105 Heckel S, Favre R, Flori J et al.. In utero fetal muscle biopsy: a precious aid for the prenatal diagnosis of Duchenne muscular dystrophy.  Fetal Diagn Ther. 1999;  14 127-132
    CrossrefPubMedGoogle Scholar
  • 106 Leturcq F, Kaplan J C. Molecular bases of dystrophinopathies.  J Soc Biol. 2005;  199 5-11
    PubMedGoogle Scholar
  • 107 Katayama S, Yano T, Takeshita N et al.. Prenatal diagnosis of Duchenne muscular dystrophy by restriction fragment length polymorphism analysis with pERT 87 intragenomic deoxyribonucleic acid probes.  Nippon Sanka Fujinka Gakkai Zasshi. 1991;  43 633-640
    PubMedGoogle Scholar
  • 108 Sekizawa A, Kimura T, Sasaki M, Nakamura S, Kobayashi R, Sato T. Prenatal diagnosis of Duchenne muscular dystrophy using a single fetal nucleated erythrocyte in maternal blood.  Neurology. 1996;  46 1350-1353
    PubMedGoogle Scholar
  • 109 Touboul D, Piednoel H, De La Porte S et al.. Changes of phospholipid composition within the dystrophic muscle by matrix-assisted laser desorption/ionization mass spectrometry and mass spectrometry imaging.  European Journal of Mass Spectrometry. 2004;  10 657-664
    CrossrefPubMedGoogle Scholar

Mert Ozan BahtiyarM.D. 

Department of Obstetrics and Gynecology, Yale University School of Medicine

333 Cedar Street, P.O. Box 208063, New Haven, CT 06520-8063