Sodium benzoate (SB) therapy is known to increase ammonia (NH3) nitrogen elimination via conjugation with glycine and excretion as urinary hippurate. In 16 children with inborn errors of urea synthesis we studied two issues: (1) the effect of chronic SB administration upon carnitine metabolism and (2) the efficacy of chronic SB therapy as measured by the molar ratio of hippurate excretion to SB intake. Measurements were performed during elective hospitalizations when the patients were in stable metabolic condition. We found that chronic SB therapy is not associated with a constant level of hippurate elimination and that interindividual and intraindividual variability may result in irregular removal of NH3nitrogen. This variability may be due to various factors including the formation of small quantities of benzoylcarnitine, which was detected in the plasma of three of four patients receiving SB and carnitine therapy and in one of two patients on SB therapy without carnitine supplementation. The ratios of acyl to free carnitine were elevated in both plasma and urine in patients not receiving carnitine supplementation, but were normal in patients receiving supplementation.

We have used peripheral blood T-lymphocyte cultures to analyze the hprt mutation in two Lesch-Nyhan syndrome males who are cousins and to confirm the carrier status of female members of the family. Both cDNA and genomic DNA sequencing studies show that this patient carries a hitherto undescribed single base deletion in the exon 5 donor splice site sequence (15:+1, δG, base number 31635). The largest cDNA product contained all nine hprt exons plus an insertion of 66 bases of intron 5, consistent with the use of a cryptic splice site in intron 5 (aag67/gtaagc). This splicing error would result in a chain terminating codon immediately after exon 5 (15:2–4, taa) and predicts a polypeptide of 133 amino acids. This loss of the normal splice donor site also results in multiple hprt mRNA species, combining the use of the cryptic splice site in intron 5 and splicing errors involving exons 2–6. In addition to defining a new Lesch-Nyhan mutation (hprtHenryville), these results provide insight into aberrant splicing of hprt mRNA in T-lymphocytes.

OBJECTIVEThis study evaluated the diagnostic accuracy of prenatal sonography in congenital diaphragmatic hernia (CDH) and assessed sonographic predictors of postnatal outcome.MATERIALS AND METHODSSonograms and medical records of 43 fetuses with CDH were retrospectively reviewed. Sonographic features were correlated to clinical evolution and surgical and pathologic findings.RESULTSCDH was diagnosed prenatally with sonography in 40 cases. Intrathoracic stomach and liver were routinely identified. Ipsilateral lung tissue could not be differentiated from herniated content. Contralateral lung was identified in all cases except two. The overall survival rate was 43% after excluding terminated pregnancies. Besides associated malformations and chromosomal anomalies, the only statistically significant predictor of survival was the quantification of the contralateral lung area at the level of an axial four-chamber view: The survival rate was 86% when the contralateral lung area was equal to or greater than one half the area of the hemithorax.CONCLUSIONSonography is highly accurate for prenatal diagnosis od CDH. Sonography also assists the prognostication of postnatal outcome in isolated CDH by allowing quantification of the contralateral lung area on a four-chamber view.

Amniocentesis was performed at 17.3 weeks in a pregnancy with severe intrauterine growth retardation. Cytogenetic studies on amniocytes were normal, 46,XX, and the pregnancy was continued. The diagnosis of Smith-Lemli-Opitz syndrome was suspected in the neonatal period and confirmed by the presence of 7-dehydrocholesterol (7-DHC) in the plasma (0.4 mmol/l, normal = not detectable) associated with a low total cholesterol concentration (0.4 mmol/l, normal = 2.56 +/- 0.23). Retrospective analysis of the amniotic fluid sample revealed an elevated level of 7-DHC (0.022 mmol/l; normal = undetectable). Therefore measurement of 7-DHC levels in amniotic fluid during the second trimester of pregnancy is useful for the prenatal diagnosis of Smith-Lemli-Opitz syndrome in families at risk and should be considered in cases of severe growth retardation of unknown aetiology for which amniotic fluid is available and in which a normal chromosomal pattern in amniocytes is present.

Amelia is a rare, usually sporadic malformation. We report on a family in which three fetuses had amelia of the upper limbs and variable deficiency of the lower limbs. The fetuses also had minor facial anomalies. Recurrence of the condition in sibs of both sexes suggests autosomal recessive inheritance. Recurrent amelia has been documented in only a few families most often associated with a different set of malformations. Possibly, mutations in more than one gene with different modes of transmission can lead to this severe limb deficiency. We speculate that the mutation found in our cases interferes with formation of the apical ectodermal ridge in the upper limbs and results in its premature degeneration in the lower limbs.

We report on 3 cases with a fetal presentation of autosomal dominant polycystic kidney disease (ADPKD), which illustrate the variable expression of ADPKD during fetal life. Fetus 1 was diagnosed at 20 weeks of gestation by ultrasonography; a molecular prenatal diagnosis was performed at 10 weeks on fetus 2, a sib of fetus 1; and ADPKD was an incidental finding in fetus 3 who was aborted at 16 weeks for anencephaly. All pregnancies were terminated and pathologic studies of the fetal kidneys were performed. From these cases and a review of the literature, we draw the following conclusions: (1) so far, all fetal ADPKD kidneys that have been histologically studied have shown cystic dilatations; 28/32 of these fetuses had ultrasonographic manifestations of the disease and/or had sibs with an early-onset form of it; (2) these cysts can be found in newly formed nephrons (fetus 2), predominantly in the more mature nephrons of the deep cortex (fetus 1) or more sparsely distributed in the cortex (fetus 3); these different patterns may reflect different rates of progression of the disease; (3) in contrast to the histologic findings in adult kidneys, glomeruli seem to be predominantly affected in fetal ADPKD; (4) severe fetal expression of ADPKD seems to cluster in some families; and (5) so far, all DNA analyses performed in families with subjects presenting during the fetal or neonatal period have been consistent with linkage to the PKD1 locus.

Intestinal and renal trehalase isozymes have been distinguished in normal human amniotic fluid on the basis of their membrane-bound character and isoelectric point (pI). The intestinal trehalase was mostly membrane bound in amniotic fluid and had a pI around 4.60. In contrast, the renal form of trehalase was soluble and had a pI around 4.37. These pI values were consistent with those found in extracts of fetal intestinal (pI 4.60) and renal (pI 4.24) tissues. The determination of trehalase isozyme composition of amniotic fluid from pathological pregnancies with anal imperforation and polycystic kidney disease confirmed our findings on the origin of amniotic fluid trehalase. In the sample from a fetus with anal imperforation, low or absent intestinal trehalase isozyme was observed whereas a higher than normal level of renal trehalase activity was found in a fetus with polycystic kidney disease.

Prenatal DiagnosisVolume 12, Issue 5 p. 439-441 Article Annex 5: List of all cytogenetic abnormalities detected D. J. Tomkins, D. J. Tomkins McMaster University, Hamilton, Ontario, CanadaSearch for more papers by this authorM. J. J. Vekemans, M. J. J. Vekemans McGill University, Montreal, Quebec, CanadaSearch for more papers by this authorI. E. Teshima, I. E. Teshima University of Toronto, Ontario, CanadaSearch for more papers by this authorD. M. Cox, D. M. Cox University of Calgary, Alberta, CanadaSearch for more papers by this authorL. Dallaire, L. Dallaire University of Montreal, Quebec, CanadaSearch for more papers by this authorR. Gagne, R. Gagne Laval University, Quebec City, Quebec, CanadaSearch for more papers by this authorD. K. Kalousek, D. K. Kalousek University of British Columbia, Vancouver, CanadaSearch for more papers by this authorJ. C. C. Lin, J. C. C. Lin University of Alberta, Edmonton, CanadaSearch for more papers by this authorV. D. Markovic, V. D. Markovic Surrey Place Centre, Toronto, Ontario, CanadaSearch for more papers by this authorM. Ray, M. Ray University of Manitoba, Winnipeg, CanadaSearch for more papers by this authorF. R. Sergovich, F. R. Sergovich University of Western Ontario, London, Ontario, CanadaSearch for more papers by this authorI. A. Uchida, I. A. Uchida McMaster University, Hamilton, Ontario, CanadaSearch for more papers by this authorH. Wang, H. Wang University of Ottawa, Ontario, CanadaSearch for more papers by this author D. J. Tomkins, D. J. Tomkins McMaster University, Hamilton, Ontario, CanadaSearch for more papers by this authorM. J. J. Vekemans, M. J. J. Vekemans McGill University, Montreal, Quebec, CanadaSearch for more papers by this authorI. E. Teshima, I. E. Teshima University of Toronto, Ontario, CanadaSearch for more papers by this authorD. M. Cox, D. M. Cox University of Calgary, Alberta, CanadaSearch for more papers by this authorL. Dallaire, L. Dallaire University of Montreal, Quebec, CanadaSearch for more papers by this authorR. Gagne, R. Gagne Laval University, Quebec City, Quebec, CanadaSearch for more papers by this authorD. K. Kalousek, D. K. Kalousek University of British Columbia, Vancouver, CanadaSearch for more papers by this authorJ. C. C. Lin, J. C. C. Lin University of Alberta, Edmonton, CanadaSearch for more papers by this authorV. D. Markovic, V. D. Markovic Surrey Place Centre, Toronto, Ontario, CanadaSearch for more papers by this authorM. Ray, M. Ray University of Manitoba, Winnipeg, CanadaSearch for more papers by this authorF. R. Sergovich, F. R. Sergovich University of Western Ontario, London, Ontario, CanadaSearch for more papers by this authorI. A. Uchida, I. A. Uchida McMaster University, Hamilton, Ontario, CanadaSearch for more papers by this authorH. Wang, H. Wang University of Ottawa, Ontario, CanadaSearch for more papers by this author First published: May 1992 https://doi.org/10.1002/pd.1970120513Citations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume12, Issue5Special Issue: Collaborative Studies on Chorion Villus Sampling in North AmericaMay 1992Pages 439-441 RelatedInformation

A 45,X/46,Xder(Y) mosaicism detected prenatally was shown to have a rare Y inversion-duplication or Y/Y translocation which can only be identified by a combination of high resolution cytogenetics and fluorescence in situ hybridization. The present data indicate the usefulness and importance of chromosome-specific probes in the identification and characterization of chromosome rearrangements.

Data on 1040 chorionic villus and 969 amniotic fluid samples were collected from women studied in the Canadian Multicentre Randomized Clinical Trial of Chorion Villus Sampling and Amniocentesis. Cytogenetic results were obtained from 98.0 per cent of chorionic villus samples and from 99.9 per cent of amniotic fluid samples. Level I mosaicism (a single cell with an abnormal karyotype) occurred frequently in both chorionic villus and amniotic fluid samples and appeared to have no clinical significance. Level II mosaicism occurred in 0.9 per cent of CVS mesenchyme and 1.5 per cent of amniotic fluid cultures and in general was not perceived to be of sufficient concern to warrant cytogenetic follow-up studies. Level III mosaicism was reported in 18 CVS cases (15 cytotrophoblast, 1 mesenchyme, and 2 with both cell methods) and in one amniotic fluid case. In all cases but one (fetus with trisomy 18), level III mosaicism was confined to the placenta. Maternal cell contamination occurring with a frequency of 6.4 per cent in the mesenchyme analyses was a concern. This study supports the final report of the Canadian Multicentre Randomized Clinical Trial of Chorion Villus Sampling and Amniocentesis. Cytogenetic analysis of chorionic villus samples appears to be an acceptable alternative to the analysis of amniotic fluid samples. However, because of mosaicism and maternal cell contamination concerns, the examination of both cytotrophoblast preparations and mesenchyme cultures from chorionic villus samples is recommended.

Prenatal DiagnosisVolume 12, Issue 5 p. 443-466 Article Annex 6: Chromosome mosaicism in CVS and amniocentesis samples I. E. Teshima, I. E. Teshima University of Toronto, Ontario, CanadaSearch for more papers by this authorD. K. Kalousek, D. K. Kalousek University of British Columbia, Vancouver, CanadaSearch for more papers by this authorM. J. J. Vekemans, M. J. J. Vekemans McGill University, Montreal, Quebec, CanadaSearch for more papers by this authorV. Markovic, V. Markovic Surrey Place Centre, Toronto, Ontario, CanadaSearch for more papers by this authorD. M. Cox, D. M. Cox University of Calgary, Alberta, CanadaSearch for more papers by this authorL. Dallaire, L. Dallaire University of Montreal, Quebec, CanadaSearch for more papers by this authorR. Gagne, R. Gagne Laval University, Quebec City, Quebec, CanadaSearch for more papers by this authorJ. C. C. Lin, J. C. C. Lin University of Alberta, Edmonton, CanadaSearch for more papers by this authorM. Ray, M. Ray University of Manitoba, Winnipeg, CanadaSearch for more papers by this authorF. R. Sergovich, F. R. Sergovich University of Western Ontario, London, Ontario, CanadaSearch for more papers by this authorI. A. Uchida, I. A. Uchida McMaster University, Hamilton, Ontario, CanadaSearch for more papers by this authorH. Wang, H. Wang University of Ottawa, Ontario, CanadaSearch for more papers by this authorD. J. Tomkins, D. J. Tomkins McMaster University, Hamilton, Ontario, CanadaSearch for more papers by this author I. E. Teshima, I. E. Teshima University of Toronto, Ontario, CanadaSearch for more papers by this authorD. K. Kalousek, D. K. Kalousek University of British Columbia, Vancouver, CanadaSearch for more papers by this authorM. J. J. Vekemans, M. J. J. Vekemans McGill University, Montreal, Quebec, CanadaSearch for more papers by this authorV. Markovic, V. Markovic Surrey Place Centre, Toronto, Ontario, CanadaSearch for more papers by this authorD. M. Cox, D. M. Cox University of Calgary, Alberta, CanadaSearch for more papers by this authorL. Dallaire, L. Dallaire University of Montreal, Quebec, CanadaSearch for more papers by this authorR. Gagne, R. Gagne Laval University, Quebec City, Quebec, CanadaSearch for more papers by this authorJ. C. C. Lin, J. C. C. Lin University of Alberta, Edmonton, CanadaSearch for more papers by this authorM. Ray, M. Ray University of Manitoba, Winnipeg, CanadaSearch for more papers by this authorF. R. Sergovich, F. R. Sergovich University of Western Ontario, London, Ontario, CanadaSearch for more papers by this authorI. A. Uchida, I. A. Uchida McMaster University, Hamilton, Ontario, CanadaSearch for more papers by this authorH. Wang, H. Wang University of Ottawa, Ontario, CanadaSearch for more papers by this authorD. J. Tomkins, D. J. Tomkins McMaster University, Hamilton, Ontario, CanadaSearch for more papers by this author First published: May 1992 https://doi.org/10.1002/pd.1970120514Citations: 44AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References Bartels, I., Hansmann, I., Holland, U., Zoll, B., Rauskolb, R. (1989). Down syndrome at birth not detected by first-trimester chorionic villus sampling, Am. J. Med. Genet., 34, 606–607. Benn, P. A., Hsu, L. Y. F. (1983). Maternal cell contamination of amniotic fluid cell cultures: results of a U.S. nationwide survey, Am. J. Med. Genet, 15, 297–305. Blakemore, K. J., Watson, M. S., Samuelson, J., Breg, W. R., Mahoney, M. J. (1984). A method for processing first-trimester chorionic villous biopsies for cytogenetic analysis, Am. J. Hum. jenet., 36, 1386–1393. Blakemore, K. J., Samuelson, J., Breg, W. R., Mahoney, M. J. (1985). Maternal metaphases on direct chromosome preparation of first trimester decidua, Hum. Genet., 69, 380. Callan, D. F., Korban, G., Dawson, G., Gugasyan, L., Krumins, E. J. M., Eichenbaum, S., Petrass, J., Purvis-Smith, S., Smith, A., Den Dulk, G., Martin, N. (1988). Extra embryonic/fetal karyotypic discordance during diagnostic chorionic villus sampling, Prenat. Diagn., 8, 453–460. Canadian Collaborative CVS-Amniocenetesis Clinical Trial Group (1989). Multicentre randomised clinical trial of chorion villus sampling and amniocentesis: first report, Lancet, 1, 1–6. Crane, J. P., Cheung, S. W. (1988). An embryogenic model to explain cytogenetic inconsistencies observed in chorionic villus versus fetal tissue, Prenat, Diagn., 8, 119–129. Hogge, W. A., Schonberg, S. A., Golbus, M. S. (1986). Chorionic villus sampling: experience of the first 1000 cases, Am. J. Obstet. Gynecol., 154, 1249–1252. Hsu, L. F., Kaffe, S., Perlis, T. E. (1987). Trisomy 20 mosaicism in prenatal diagnosis–a review and update, Prenat. Diagn., 7, 581–596. Jackson, L., Wapner, R., Barr, M., Hux, C., Davis, G. (1985). Maternal contamination of chorionic villus samples: comparison between direct preparation and culture, Am. J. Hum. Genet., 37 (Suppl.), A99. Jensen, P. K. A., Hertz, J. M., Therkelsen, A. J. (1986). Admixture of maternal metaphases in first trimester direct chromosome preparations?, Prenat. Diagn., 6, 383–385. Kalousek, D. K. (1988). The role of confined chromosomal mosaicism in placental function and human development, Growth, Genet. Hormones, 4, 1–3. Kalousek, D., Dill, F. (1983). Chromosomal mosaicism confined to the placenta in human conceptions, Science, 221, 665–667. Kalousek, D. K., Dill, F. J., Pantzer, T., McGillivray, B., Yong, S. L., Wilson, R. D. (1987). Confined chorionic mosaicism in prenatal diagnosis, Hum. Genet., 77, 163–167. Ledbetter, D. H., Martin, A. O., Verlinsky, Y., Pergament, E., Jackson, L., Yang-Feng, T., Schonberg, S. A., Gilbert, F., Zachary, J. M., Barr, M., Copeland, K. L., DiMaio, M. S., Fine, B., Rosinsky, B., Schuette, J., de la Cruz, F. F., Desnick, R. J., Elias, S., Golbus, M. S., Goldberg, J. D., Lubs, H. A., Mahoney, M. J., Rhoads, G. G., Simpson, J. L., Schlesselman, S. E. (1990). Cytogenetic results of chorionic villus sampling: high success rate and diagnostic accuracy in the United States collaborative study, Am. J. Obstet. Gynecol., 162, 495–501. Martin, A. O., Elias, S., Rosinsky, B., Bombard, A. T., Simpson, J. L. (1986). False-negative finding on chorionic villus sampling, Lancet, 2, 391–392. Reddy, K. S., Peterson, M. B., Corson, V., Escallon, C., Antonarakis, S. E., Blakemore, K. J. (1990). The vanishing twin: an explanation for discordance between CVS karyotype and fetal phenotype using chromosome markers and DNA studies, Am. J. Hum. Genet., 47 (Suppl.), A284. Simoni, G., Brambati, B., Danesino, C., Rossella, F., Terzoli, G. L., Ferrari, M., Fraccaro, M. (1983). Efficient direct chromosome analyses and enzyme determinations from chorionic villi samples in the first trimester of pregnancy, Hum. Genet., 63, 349–357. Tharapel, A. T., Elias, S., Shulman, L. P., Seely, L., Emerson, D. S., Simpson, J. L. (1989). Resorbed co-twin as an explanation for discrepant chorionic villus results: non-mosaic 47,XX,+16 in villi (direct and culture) with normal (46,XX) amniotic fluid and neonatal blood, Prenat. Diagn., 9, 467–472. Vejerslev, L. O., Mikkelsen, M. (1989). The European collaborative study on mosaicism in chorionic villus sampling: data from 1986 to 1987, Prenat. Diagn., 9, 575–588. Vekemans, M. J. J., Perry, T. B. (1986). Cytogenetic analysis of chorionic villi: a technical assessment, Hum. Genet., 72, 307–310. Williams, J., Medearis, A. L., Chu, W. H., Kovacs, G. D., Kaback, M. M. (1987). Maternal cell contamination in cultured chorionic villi: comparison of chromosome Q-polymorphisms derived from villi, fetal skin and maternal lymphocytes, Prenat. Diagn., 7, 315–322. Wirtz, A., Seidel, H., Brusis, E., Murken, J. (1988). Another false-negative finding on placental sampling, Prenat. Diagn., 8, 321. Worton, R. G., Stern, R. (1984). A Canadian collaborative study of mosaicism in amniotic fluid cell cultures, Prenat. Diagn., 4, 131–144. Citing Literature Volume12, Issue5Special Issue: Collaborative Studies on Chorion Villus Sampling in North AmericaMay 1992Pages 443-466 ReferencesRelatedInformation

Prenatal DiagnosisVolume 12, Issue 5 p. 473-476 Article Annex 8: Familial chromosomal aberrations and metabolic disorders J. L. Hamerton, J. L. Hamerton University of Manitoba, Winnipeg, CanadaSearch for more papers by this authorL. Dallaire, L. Dallaire University of Montreal, Quebec, CanadaSearch for more papers by this authorD. Tomkins, D. Tomkins McMaster University, Hamilton, Ontario, CanadaSearch for more papers by this authorA. Lippman, A. Lippman McGill University, Montreal, Quebec, CanadaSearch for more papers by this author J. L. Hamerton, J. L. Hamerton University of Manitoba, Winnipeg, CanadaSearch for more papers by this authorL. Dallaire, L. Dallaire University of Montreal, Quebec, CanadaSearch for more papers by this authorD. Tomkins, D. Tomkins McMaster University, Hamilton, Ontario, CanadaSearch for more papers by this authorA. Lippman, A. Lippman McGill University, Montreal, Quebec, CanadaSearch for more papers by this author First published: May 1992 https://doi.org/10.1002/pd.1970120516Citations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume12, Issue5Special Issue: Collaborative Studies on Chorion Villus Sampling in North AmericaMay 1992Pages 473-476 RelatedInformation

During a follow-up study of 19,790 pregnancies at risk for a genetic disease, from 1968 to 1989, 1083 fetuses were found to have an anomaly during the second trimester, leading to 977 terminations of pregnancy. Neural tube defects (31.4 per cent), chromosomal disorders (27.1 per cent), and Mendelian or multifactorial diseases (10.6 per cent) were the main causes of fetal anomaly. More than half (52.9 per cent) of the fetal anomalies were detected by routine ultrasound examination. Forty-two per cent of cystic hygromas were secondary to a chromosomal defect. We stress the importance of a comprehensive fetal and newborn examination to ensure an accurate diagnosis so that subsequently accurate counselling can be provided.

Ultrasonographic determination of biparietal diameter/femur length ratios performed at 16 or 17 weeks' gestation in fetuses with trisomy 21 were not statistically different from those of 155 normal fetuses. It appears that this test could not be used for screening for trisomy 21.