A major study on the use of chorionic villi sampling (CVS) is "Medical Research
Council European trial of chorion villus sampling", Lancet
337: 1491-9. An editorial on the use of CVS is in Lancet
337: 1513-5. The trials of CVS in several countries are compared. Letters on limb
abnormalities and CVS are in Lancet
337: 762-3, 1091-2, 1422-4; 338: 51, 196. There may well be some association here,
but the reports appear to vary among different groups. Other methods should also
be studied, in order to determine the best and safest option. CVS has the advantage
of earlier screening time, but the risk that is caused by the technique of spontaneous
abortion, is under some question.
A review of a book Karen Filkins & J. Russo, eds., Human Prenatal Diagnosis , 2nd ed. (624pp., US$150, NY: Marcel Dekker 1990) is in AJHG 48: 1217-8 & NEJM 324: 1675. It is not very favourable, saying that the book is varied in its coverage, and focuses on recombinant DNA techniques, but is an information source. On the safety of magnetic resonance imaging and warnings over its use see BMJ 303: 205. More comments on prenatal care and problems are in BMJ 302: 1390-4, 1526-30, 1454-8, 1592-6; 303: 111-5.
Comment on the use of maternal alpha-fetoprotein screening are in NEJM 325: 55-7, and a paper is; D.K. Waller et al., "Second trimester maternal serum alpha-fetoprotein levels and the risk of subsequent fetal death", NEJM 325: 6-10. See also AJHG 48: 1201-4. There is an association between high levels of this protein and fetal death, and the death can occur late in pregnancy. Letters on the estimation of Down's syndrome appear in BMJ 302: 1536-7; 303: 54-56. A review on the role of chromosome 21 in Down's syndrome and Alzheimer's disease is in AJHG 48: 1192-1200. On Alzheimer's disease and Parkinson's disease news see Science 252: 1380-1. On motor neuron diseases see NS (17 Aug 1991), 21-5.
A review on the PCR is H.A. Erlich et al., "Recent advances in the Polymerase Chain reaction", Science 252: 1643-50. It discusses the advances in instrumentation, methodology and the range of applications of PCR. It includes mention of the diagnosis and forensic uses of PCR, as well as research. The use of PCR for clinical diagnosis of Pneumocystis carinii is reported in Lancet 337: 1378-9. On the analysis of haemophilia A using PCR techniques see Lancet 338: 207-11.
A review including a extensive tabulation of genetic disease probes (2687 reports)
is D.N. Cooper & J. Schmidtke, "Diagnosis of genetic disease using recombinant DNA.
Third edition", Human Genetics
87: 517-60. For those who require an updated list, the authors can be contacted,
and a computer database is setup. In total the probes listed can analyse 152 dominant,
82 recessive, and 70 X-linked diseases.
A general comment on the use of maternal screening for neural tube defects and Down's syndrome in Australia is in MJA 155: 67-8, 115-7. The cost of screening is said to be A$32 per patient. The wider use of screening is encouraged. On a strategy for the screening of Down's syndrome based on individual risk see BMJ 303: 551-3. On ways to assess the seriousness of Down's syndrome see C.J. Epstein et al., "Protocols to establish genotype-phenotype correlations in Down Syndrome", AJHG 49: 207-35. See also BMJ 303: 312-3, 468-9, 715; Obstetrics & Gynecology 78: 257-62. On the health of pregnant women see BMJ 303: 460-2.
On the use of chorionic villi sampling see Lancet 338: 449-50, 776; Br. J. Obstetrics & Gynecology 98: 849-52.. On the possibility of using early amniocentesis for screening see Lancet 338: 750-1.
On prenatal diagnosis of cystic fibrosis see Lancet 338: 458. On the positive uptake of cystic fibrosis screening in the U.K. see BMJ 303: 504-7; see also Amer. J. Medical Sciences 302: 142-4, AJHG 49: 240-2. On treatment for cystic fibrosis see NEJM 325: 575-7. On prenatal screening for hemoglobinpathies see AJHG 49: 466-7. A short review on products for mutation detection is in Nature 353: 582-3. On risk calculations in Fragile-X syndrome see AJMG 40: 523.
A review of the U.K. neonatal screening programs for phenylketonuria is in BMJ 303: 333-5, and see p.716 for letters on this topic. On neonatal screening in general see NEJM 325: 802-4, and on cystic fibrosis see K.B. Hammond et al., "Efficacy of statewide neonatal screening for cystic fibrosis by assay of trypsinogen concentrations", NEJM 325: 769-74. Their program was successful, scientifically, at detecting affected individuals which could than be treated. Screening for abnormal protein levels avoids the problem of genetic heterogeneity of the minor mutations of CF when using DNA probes in genetic screening.
The ligase chain reaction (LCR) may have many more applications in genetic diagnostics than the PCR; Science 254: 1292-3. It can be used to simultaneously screen for several genetic diseases in the same test tube, because it is more easily automated and may be more reliable. LCR only applifies the sequences that are being screened for, unlike PCR which amplifies all the sequence between two primers.
Data relevant for genetic counseling for deafness is in Z. Brownstein et al., "Estimated number of loci for autosomal recessive severe nerve deafness within the Israeli Jewish population, with implications for genetic counseling", AJMG 41: 306-12.
A new method for chromosomal analysis which produces a much quicker result than the older method used with amniocentesis or chorionic villi sampling (CVS); Science 254: 378-9. It is abbreviated FISH, fluorescent in situ hybridisation. There is also research on using fetal cells in maternal blood for screening, but clinical trials may be 2 years away. On dangers of CVS see BMJ 303: 936-7.
The epidemiology of Down's syndrome in South Australia from 1960-89 is presented in AJHG 49: 1014-24. Extension of prenatal screening for Down's syndrome to Trisomy-18 is discussed in AJHG 49: 1025-33. On cholesterol screening see JAMA 266: 2701-2.
On general techniques for DNA screening and testing for transcription of transferred genes see Biotechnology 10: 36-9. Also see Nature 355: 280-2 for some new technical kits for screening methodology. On the progress in PCR technology see a short review of the use of SELEX (systematic evolution of ligands by exponential enrichment) in Biotechnology 10: 137-40.
On the screening methods for Down"s syndrome and establishing a European network see Lancet 338: 1516. A letter on the risks of Down's syndrome and the rate of amniocentesis is in BMJ 304: 252.
On the many uses of ultrasound (see also section on fetal environment) see FDA Consumer (Dec 1991), 34-9. A study suggesting that prenatal care for high risk patients can reduce the fetal death rate is in Obstetrics & Gynecology 79: 40-5.
On the costs and benefits of preemployment drug screening see JAMA 267: 52, 91-3.
Preimplantation genetic diagnosis to analyse a specific disease has resulted in a birth of a baby in mid-March, in the UK. The analysis was the result of collaboration between Hammersmith Hospital in London, and geneticists at Baylor College in Houston, Texas. It appears that an unrelated private clinic, the Genetics and IVF Institute in Fairfax, Virginia, is already offering such diagnostic services for a fee, which could be said to be very premature; BME (March 1991), 7. Patient views of preimplantation diagnosis are presented in Prenatal Diagnosis 11 (1991), 493-500.
A discussion on how to maintain high standards of genetic services in the USA is A. Milunsky, "Threatened survival of academic-based genetic laboratory services", AJHG 50: 643-5. A new widely acclaimed book by A. Milunsky is Heredity and Your Family's Health (Johns Hopkins University Press 1992, 508pp., US$19). In July the third edition of his textbook Genetic Disorders and the Fetus: Diagnosis, prevention and Treatment will be published, including several chapters on ethical and legal issues of genetic counseling.
A paper reporting several cases of chorionic villi sampling ( CVS )-induced deformities among 3000 cases examined is R. Schloo et al., "Distal limb deficiency following chorionic villi sampling", AJMG 42: 404-13. A method for using ultrasound to screen for chromosomal defects is K.H. Nicolaides et al., "Fetal nuchal translucency: ultrasound screening for chromosomal defects in first trimester of pregnancy", BMJ 304: 867-9. Screening for hearing loss in high risk neonates is described in BMJ 304: 806-9. Failures of neonatal screening tests are discussed in JAMA 267: 1095-9.
A method to enhance the performance of the PCR is described in Biotechnology 10: 413-7. A review of DNA analysis is Y.W. Kan, "Development of DNA analysis for human diseases. Sickle cell anemia and thalassemia as a paradigm", JAMA 267: 1532-6.
The possibility to perform gene manipulation on plastic plates is a new method described in Nature 357: 519-20. On a history of medical genetics by V. McKusick see AJHG 50: 663-70.
The question of lowering the age for amniocentesis to detect chromosome abnormalities after maternal alpha-fetoprotein screening is discussed in AJMG 42: 801-6. On the performance of aminocentesis see Obs & Gyn 79: 940-4. Some claim that the risks of chorionic villi sampling are no more than amniocentesis, see Asia-Oceania J. Obstet. Gynecol. 18: 31-5; Lancet 339: 876-7. The use of CVS for fetal Rh typing is discussed in Amer. J. Obs. Gynecol. 166: 1407-11. On the use of magnetic cell sorting as a method for prenatal diagnosis from maternal blood samples see Amer. J. Obstet. Gynecol. 166: 1350-5. The use of Doppler ultrasound is discussed in Lancet 339: 1083-4.
Public opinion regarding screening policies for carriers are discussed in JMG 29: 313-9. On the development of cystic fibrosis screening information see JMG 29: 308-12. On genetic testing for hemoglobinpathies in Sicily, Lancet 339: 1361-2.
A report on the alternatives to PCR that are being developed and will soon be commercially available is in GEN 12(9), 1, 8. The commercial development of genetic testing procedures is discussed in GEN 12(8), 20, 27. Still about half the genetic testing done in the USA is done in academic environments. A letter on the economics of clinical genetic services in academic institutions is in AJHG 50: 1351-2. A letter asking who should pay for children with genetic diseases whose parents don't want to use testing (while saying all should get care) is in Lancet 339: 1614-5. Also see experiences from Hungary in A.E. Czeizel et al., "The check-up of reproductive health and genetic counseling", Genetic Counseling 3: 61-6.
Saliva is becoming a very common diagnostic sample; BMJ 305: 207-8, and may replace blood in many tests. Even better for the squeamish may be breath, see M. Phillips, "Breath tests in medicine", SA (July 1992), 52-7.
Comments on the use of FISH , and the accuracy are in NEJM 326: 1638-40. A paper reporting some trials is K. Suzumori et al., "Fetal cells in the maternal circulation: detection of Y-sequence by gene amplification", Obs. & Gyn. 80: 150-4. A paper calling for aminocentesis at 12 weeks of pregnancy to be considered a viable option is F.W. Hanson et al., "Early amniocentesis: outcome, risks, and technical problems at <12.8 weeks", Amer.J. Obs. & Gyn. 166: 1707-11. Also, F. Stener Jorgensen et al., "Genetic amniocentesis at 7-14 weeks of gestation", Prenatal Diagnosis 12: 277-83.
A method extending the number of genetic tests that can be made from a single cell is described in L. Zhang et al., "Whole genome amplification from a single cell: Implications for genetic analysis", PNAS 89: 5847-51. A review including a list of some US institutions developing embryonic biopsy methods was presented at the Toronto Health Law and Ethics meeting in July, by Dr A.L. Bonnicksen (Dept. of Political Science, Northern Illinois University, DeKalb, IL 60115, USA). Several diseases are targetted already in the experimental protocols. See also JAMA 268: 727-9.
Papers on improved methods for Down's syndrome screening are: N. Wald et al., "First trimester concentrations of pregnancy associated plasma protein A and placental protein 14 in Down's syndrome", BMJ 305: 28; T. Bryndorf et al., "New rapid test for prenatal detection of trisomy 21 (Down's syndrome): preliminary report", BMJ 304: 1536-9; R.G. Ryall et al., "Improved performance in a prenatal screening programme for Down's syndrome incorporating serum-free hCG subunit analyses", Prenatal Diagnosis 12: 251-61; BMJ 305: 425. Data on the incidence of spina bifida in the USA is in JAMA 268: 708-9.
A method that is claimed to be effective for "sex" selection of sperm is S.A. Ishijima et al., "Separation of X- and Y-chromosome-bearing murine sperm by free-flow electrophoresis: evaluation of separation using PCR", Zoological Science 9: 601-6.
The use of preimplantation diagnosis for cystic fibrosis is reported in A.H. Handyside et al., "Birth of a normal girl after in vitro fertilization and preimplantation diagnostic testing for cystic fibrosis", NEJM 327: 905-9, 951-3. Detection of fetal DNA in maternal blood is described in Obs & Gyn 80: 601-3.
In the Netherlands all women over 36 years of age can have CVS or aminocentesis, but it is estimated that one half of the women actually use it; Network (Aug 1992), 5-7.
The use of three proteins as a screening test for Down's syndrome for routine use is called for in J.E. Haddow et al., "Prenatal screening for Down's syndrome with use of maternal serum markers", NEJM 327: 588-93; O.P. Phillips et al., "Maternal serum screening for fetal Down syndrome in women less than 35 years of age using alpha-fetoprotein, hCG, and unconjugated estriol: A prospective 2-year study", Obs & Gyn 80: 353-8. On the blood testing of 3 compared to 2 indicative proteins for routine antenatal screening for Down's syndrome see BMJ 305: 768-71; Lancet 340: 799. Use of PCR for Down's syndrome screening is reported in Lancet 340: 620-1.
The question of when and how to perform prenatal diagnosis is the subject of an editorial in NEJM 327: 636-8. It follows major studies on prenatal screening, including; L.G. Jackson et al., "A randomized comparison of transcervical and transabdominal chorionic-villus sampling", NEJM 327: 594-8. Both methods of CVS were found to be equally safe, based on diagnosis of 3,999 women at 7-12 weeks gestation. The rate of using either method of CVS is reported in Obs & Gyn 80: 349-52. A higher incidence of limb abnormalities and CVS is still questioned by many as discussed in Lancet 340: 668, 785. A review of studies is J.L. Halliday et al., "Importance of complete follow-up of spontaneous fetal loss after amniocentesis and chorion villus sampling", Lancet 340: 886-90.
The use of ultrasound is discussed in K.H. Nicolaides et al., "Ultrasonographically detectable markers of fetal chromosomal abnormalities", Lancet 340: 704-7. Aftermore than 2000 cases of detecting abnormalities with ultrasound they report which abnormalities were detected, as a guide to what others should look for. The use of first trimester transabdominal fetoscopy is reported in Lancet 340: 429. The use of rapid DNA sequence analysis as a method of clinical genetic diagnosis is reported in SA (Oct 1992), 93. Commercial investment in genetic testing, and the US company IG labs, is discussed in Bio 10: 1080. Competitive PCR is reviewed in Nature 359: 557-8.
A review of screening for beta-thalassemia amongst the Italian population is in Human Genetics 89: 585-9. Fragile X diagnosis methods are reported in JMG 29: 726-9. Hemophilia B and genetic counseling are discussed as a model disease in JMG 29: 601-7. A book review of interest for general reading is in Lancet 340: 838.
Preimplantation diagnosis is discussed in a book review in JMG 29: 840. A Danish study of amniocentesis and CVS has found trans abdominal CVS is safer than transcervical CVS; and it had the same rate of fetal loss, Lancet 340: 1237-44. Encouraging results on the use of maternal blood fetal cell sampling for Down's syndrome diagnosis are in Lancet 340: 1033. Restraint in the use of fetal blood sampling is urged in Obs. & Gyn. 80: 873-7. Products for fluorescent DNA detection are reviewed in Nature 359: 859-61. Ligation-anchored PCR is described in PNAS 89: 9823-5.
A comprehensive 29 chapter work covering the various methods of prenatal diagnosis, in addition to two chapters on ethical or legal issues is A. Milunsky, ed., Genetic Disorders and the Fetus. Diagnosis, Prevention, and Treatment, 3rd edition (John Hopkins Univ. Press, 1992, 992pages, 78). Also on prenatal screening see Lancet 340: 1006-7. General reviews on population screening for cystic fibrosis are AJHG 51: 943-50, 951-6; Lancet 340: 984. Serum alpha-fetoprotein levels and midtrimester placental abnormalities can be used to predict poor pregnancy outcome; AJOG 167: 1032-7. Letters on Down's screening are in Lancet 340: 1034; BMJ 305: 1017-8, 1228; and on the safety of CVS Lancet 340: 1034. A genetic test for inherited thyroid cancer is possible; NS (14 Nov 1992), 17.
A discussion of the qualifications "necessary" for genetic counseling see AJHG 51: v-vii. The American Board of Human Genetics is considering splitting based on those who have or do not have M.D. qualifications - to exclude those without M.D.'s so that the society can be recognised as part of the board of medical specialities. Such professional qualifications would seem to have little to do with being a good genetic counselor. On academic and private genetic services see AJHG 51: 890-5, 910-112.
A review on the use of molecular methods for infectious disease detection is in NEJM 327: 1290-7. A test for Chagas' Disease is in Biotechnology 10: 1474-7. The development of a non-invasive screening light "Dream Beam" for glucose level measurements that diabetics can use is described in Science 258: 892-3.
A general review of prenatal diagnosis is in NEJM 328: 114-20. A further study reporting limb abnormalities following CVS is P. Mastroiacovo et al., "Limb abnormalities following chorionic villus sampling: A registry based case-control study", AJMG 44 (1992), 856-64. A smaller first trimester fetus has been found to be at increased risk of chromosome abnormalities; AJOG 167: 1525-8.
A non-invasive test for cystic fibrosis is available in the USA, marketted by IG Laboratories; GEN (Dec 92), 32. It uses a cheek brush (brushing some of the loose cells from the inside of the mouth), and tests fro the 16 most common mutations. The new head of the US NIH genome project, F. Collins, has called for an urgent need for mass screening for breast cancer, to avoid the delays experienced in CF; NS (6 Feb 1993), 5. A proposal for disclosure couple screening as a method for CF screening in the population is suggested in JMG 30: 86-8. (see also the above section). Reporting the results of CF carrier screening is discussed in AJOG 168: 1-6.
Newborn screening for Duchenne muscular dystrophy has been found to be acceptable to parents at risk, as it lowers the emotional stress of waiting to know if the child is affected, D.M. Bradley et al., "Experience with screening newborns for Duchenne muscular dystrophy in Wales", BMJ 306: 357-60, 349.
The use of portable glucose monitors is reported to be useful for diabetes patients at home in MJA 157 (1992), 446-8. The enhancement of education about diabetes by the use of computers is reported in MJA 157 (1992), 489-91. The merits of home cholesterol testing are discussed in Lancet 340 (1992), 1386.
A reduction to the age 30 years for general amniocentesis is refuted by UK counselors in a letter in AJMG 45: 395. A paper reviewing trials of early amniocentesis (10-14 weeks of gestation) finds that the technique is similar to late amniocentesis, and recommends its use; Prenatal Diagnosis 13: 21-7. A paper reporting results of fetal blood sampling as a means of detecting cytogenetic abnormalities recommends its use under certain conditions; Prenatal Diagnosis 13: 1-8. The results of 2574 cases of CVS in a US clinic are summarised in AJMG 45: 361-4. On estimating limb abnormalities following CVS see AJMG 45: 529; Lancet 341: 468-9, 500. On prenatal screening and chromosome abnormalities see AJMG 45: 394.
The conclusion that we can prevent many genetic diseases, and estimates for the proportions, by genetic screening is made in A.E. Czeizel et al., "What proportion of congenital abnormalities can be prevented?", BMJ 306: 499-503, 857-8. The question whether we should offer prenatal diagnosis to all pregnant women is recommended in O&G 81: 615-8. The access to prenatal care for poorer women in the USA is still poor; P. Braveman et al., "Access to prenatal care following major Medicaid eligibility expansions", JAMA 269: 1285-9. A book review on the history of medical genetics in Canada is in AJMG 45: 668-9. Trends in the births of people with Down's syndrome in the UK are in BMJ 306: 431-2, 650, 791-2. Fetal ultrasonography is being increasingly used in diagnosis, as are biochemical tests.
A cost comparison of two methods for population cystic fibrosis screening is in AJHG 52: 616-26. The cheaper method would cost about US$10,000 per case. Letters on the suitability of population screening for Fragile X in the UK are in Lancet 341: 769-70. A DNA-specific probe for diagnosis of myotonic dystrophy is described in NEJM 328: 471-5. Difficulties in the use of PCR for hepatitis C diagnosis are reported in Lancet 341: 722-4.
A home test for cholesterol has just been approved by the FDA in the USA, that is expected to sell for US$10-15 each; Time (15 March 1993), 15. In the USA many opportunities for testing are missed, and less than one third of people at risk see doctors; JAMA 269: 1133-8. The question of whether cholesterol tests should be offered to young people is debated in JAMA 269: 1426-7. An enzyme, phospholipase 1 or 2, implant to reduce cholesterol levels has been found to be effective; NS (13 Feb 1993), 18.
The possibility of a breath test for cancer is discussed in Science 259: 1394-8. Screening for prostrate cancer is discussed in NS (6 Feb 1993), 27-30.
A review of PCR in medicine is BMJ 306: 441-6. A letter on Doppler ultrasound for prenatal tests is Lancet 341: 501-2. A review of magnetic resonance imaging is in NEJM 328: 708-16. The use of the enzyme RNA Polymerase for research, and biological functions, are discussed in Science 259: 944-5. Techniques to isolate RNA from whole blood allow the possibility of RNA-based diagnostics ; Nature 362: 186-8.
The use of FISH to rapidly identify chromosomal abnormal-ities is reported in B.E. Ward, et al., "Rapid prenatal diagnosis of chromosomal aneuploidies by fluorescence in situ hybridization: Clinical experience with 4,500 specimens", AJHG 52: 854-65, p. 851-3. The suggest that it is an effective addition to the analysis of uncultured amniocytes. A Japanese research team has developed a high speed automatic diagnostic system which can detect chromosome disorders. The system can process 240 lymphocytes a day with a diagnostic accuracy of 98%; GEN (1 May 1993), 32.
Bad timing of CVS is linked to birth defects; NS (10 April 1993), 12-3. A book review of Prenatal Diagnosis and Screening is in BMJ 306: 1623. Letters on prenatal diagnosis are in NEJM 328: 1710-2.
Low maternal serum levels of plasma protein A in the first trimester can be used as an early risk diagnosis of pregnant women; Br. J. Obstetrics & Gynaecology 100: 324-6. The effects of wrongly calculated maternal age on serum screening are shown in BMJ 306: 1509-11. On screening for Down's syndrome see BMJ 306: 1198-9, 1541, 1616; Br. J. Obstetrics & Gynaecology 100: 430-5. Rhesus status of the fetus may also be detected by maternal blood sampling, Lancet 341: 1147-8. An in utero fetal muscle biopsy is reported in AJMG 46: 309-312. Complications of fetal blood sampling, a 1.4% miscarriage rate, are reviewed in AJOG 168: 1339-44.
Screening for hemochromatosis, a genetically linked iron deposition disease, is reviewed in NEJM 328: 1616-20. Screening for lipid disorders is reviewed in NEJM 328: 1269-70; for heart disease in Japanese children, in BMJ 306: 1128; and for colorectal cancer screening by fecal blood in NEJM 328: 1365-71, 1416-7. general cautious comments on screening are in BMJ 306: 1222-3.
A comment on whether the new paradigms of molecular medicine can be introduced to the USA is in Lancet 341: 1379-80. A review of molecular medicine by C.T. Caskey is in JAMA 269: 1986-92, including detection methods. A technical description of immuno-PCR with a commercial avidin-based system is in Science 260: 698-9.
A technique allowing identification of DNA in small blood samples within 2-3 hours has been reported by Prof. Isao Karube, Research Center for Advanced Science and Technology, University of Tokyo, Japan. A review of methods for detecting single base mutations is TIBTECH 11: 238-46. DNA amplification is discussed in Biotechnology 11: 940-2; and PCR on pp. 938-9; and for sex testing,Lancet 341: 1593. The direct colorimetric detection of ligands for bioassays is in Science 261: 585-8.
The American College of Medical Genetics statement on FISH is AJHG 53: 526-7. On improving the quality of CVS; AJOG 168: 1766-7, and on limb defects and CVS , AJMG 46: 483-5. The lower use of fetal blood sampling due to other techniques is in BMJ 307: 143-4. A review of the use of imaging is Science 261: 554-61. Anxiety is a factor found with imaging, JAMA 270: 745-7.
The economics of prenatal screening are in V. Seror et al., "Economic assessment of maternal serum screening for Down's syndrome using human chorionic gonadotropin", Prenatal Diagnosis 13: 281-92. On first trimester alpha-fetoprotein screening for Down's syndrome, Prenatal Diagnosis 13: 215-18; AJOG 168: 1864-9. On chorionic gonadotropin, AJOG 168: 1852-7. On the current practice of hemoglobin mutation screening in Ontario, CMAJ 148: 1481-5; see also pp. 1975-9. In Ontario about 80 prenatal tests are done annually for 360 pregnancies at risk. The use of a chromo-some 18 specific probe for preimplantation diagnosis may require at least two cells for more reliable results; Human Reproduction 8: 296-301; see also Lancet 342: 403-4. Fetal cell sampling from maternal blood has been reported to be used at Kanazawa Medical College in Japan, Yomiuri Shinbun (15 Aug 1993), 1.
The cost effectiveness of neonatal screening for Duchenne muscular dystrophy was found to be C$172,000 total cost per case avoided; SSM 37: 541-7.
A model for population genetic screening is in JMG 30: 580-2. The use of PCR for population screening is considered viable in Lancet 341: 1591-2. A retrospective review of genetic carrier testing for hemophilia is SSM 37: 639-48. On cystic fibrosis screening, JMG 30: 621; Clin. Genetics 44: 44-5; AJMG 46: 665-9.
Pregnancy screening for cystic fibrosis is discussed following preliminary results of pilot studies in Lancet 342: 569-70, 624; BMJ 306: 1580-3, 1584-6; 307: 849-52. A report on the practice of Tay Sachs counseling is E. Broide et al., "Screening for carriers of Tay-Sachs disease in the ultraorthodox Ashkenazi Jewish community in Israel", AJMG 47: 213-5. Carriers are detected, and encouraged not to marry, while preserving anonymity.
Antenatal screening for Down's syndrome is discussed in K. Spencer & P. Carpenter, "Prospective study of prenatal screening for Down's syndrome with free b-human chorionic gonadotrophin", BMJ 307: 764-9; BMJ 307: 679-80. On serum screening, AJHG 53: 777-9; BMJ 307: 500-2. A general method to look for cryptic chromosomal abnormalities is described in AJHG 63: 688-701. The use of fetal leg and femur/foot length ratios as a marker for Down's syndrome is described in AJOG 169: 557-63.
A review of A. Milunsky, ed., Genetic Disorders and the fetus: Diagnosis, Prevention and Treatment (Third Edition) is AJHG 53: 788-9. A paper on the economic analysis of antenatal screening is in SSM 37: 873-8.
The use of PCR to detect Fragile X is reported in T. Brown et al., "Rapid Fragile X carrier screening and prenatal diagnosis using a nonradioactive PCR test", JAMA 270: 1569-75. The isolation of molecular sex markers for new species is reported in PNAS 90: 8324-6. The use of DNA amplification to determine fetal rhesus type from amniotic cells is reported in NEJM 329: 607-10, 658-60. It avoids fetal blood sampling. The inventor of the PCR, K.B. Mullis shared the 1993 Nobel Prize for Chemistry; Nature 365: 685. On PCR monitoring, Biotechnology 11: 1026-30.
A paper looking at the cost effectiveness of neonatal muscular dystrophy screening is SSM 37: 541-7.