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Prenatal diagnosis of haemophilia: our experience of 44 cases

  • Federica Zarrilli , Veronica Sanna , Rosaria Ingino , Rita Santamaria , Angiola Rocino , Antonio Coppola , Giovanni Di Minno EMAIL logo und Giuseppe Castaldo
Veröffentlicht/Copyright: 16. Juli 2013
Clinical Chemistry and Laboratory Medicine (CCLM)
Aus der Zeitschrift Clinical Chemistry and Laboratory Medicine (CCLM) Band 51 Heft 12

Abstract

Background: Haemophilia A and B (HA, HB) are the most frequent X-linked bleeding diseases; two-thirds of cases are severe.

Methods: We counselled 51 couples for prenatal diagnosis (PD) of haemophilia. In 7/51 (13.7%) cases, the couple decided not to undergo PD because counselling revealed that they were carriers of a mild form of the disease, while we performed 44 PD for severe HA (36 cases) or HB (8 cases). The indication for PD was a haemophilic child (30/44, 68.2%) or an affected family member (12/44, 27.3%); in two cases the non-carrier mother of isolated haemophilic patients requested PD because of the risk of mosaicism.

Results: We completed PD in 43/44 cases; in one case, the prenatal sample was contaminated by maternal DNA; however, molecular analysis revealed the female sex of the foetus. We performed PD for 16 of the 36 couples at risk of HA (44.4%) by analysing the intron (IVS)22 inversion; in 1/36 cases (2.8%) the mother had the IVS1 inversion, and in 8/36 (22.2%) the family mutation was identified by sequencing; in 11/36 (30.6%) cases the family mutation was unknown, and PD was performed by linkage (no recombination nor uninformative cases occurred). For HB, in 6/8 (75.0%) cases, PD was performed by DHPLC or by sequencing; in 2/8 cases we tested intragenic markers (again with no cases of recombination or uninformative families).

Conclusions: PD in well-equipped laboratories, and multidisciplinary counselling are an aid to planning reproductive and early therapeutic strategies in families with severe haemophilia.

Keywords: amniocentesis; chorionic villi; F8C ; F9 ; haemophilia; prenatal diagnosis
Corresponding author: Giovanni Di Minno, MD, PhD, Dipartimento di Medicina Clinica e Chirurgia, Università di Napoli Federico II, Via S. Pansini 5, 80131, Naples, Italy, E-mail:

Grants from the Regione Campania (DGRC 1901/09) are gratefully acknowledged. We are indebted to Jean Ann Gilder (Scientific Communication srl) for editing the text.

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

References

1. Castaldo G, D’Argenio V, Nardiello P, Zarrilli F, Sanna V, Rocino A, et al. Haemophilia A: molecular insights [review]. Clin Chem Lab Med 2007;45:450–61.10.1515/CCLM.2007.093Suche in Google Scholar PubMed

2. Castaldo G, Nardiello P, Bellitti F, Santamaria R, Rocino A, Coppola A, et al. Haemophilia B: from molecular diagnosis to gene therapy [review]. Clin Chem Lab Med 2003;41: 445–51.10.1515/CCLM.2003.067Suche in Google Scholar PubMed

3. Santacroce R, Acquila M, Belvini D, Castaldo G, Garagiola I, Giacomelli SH, et al. Identification of 217 unreported mutations in the F8 gene 3 in a group of 1,410 unselected Italian patients with hemophilia A. J Hum Genet 2008;53:275–8.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000253572300011&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f310.1007/s10038-007-0238-ySuche in Google Scholar PubMed

4. Belvini D, Salviato R, Radossi P, Pierobon F, Mori PG, Castaldo G, et al. Molecular genotyping of the Italian cohort of patients with haemophilia B. Haematologica 2005;90:635–42.Suche in Google Scholar PubMed

5. Castaldo G, Nardiello P, Bellitti F, Rocino A, Coppola A, Di Minno G, et al. Denaturing HPLC procedure for factor IX gene scanning. Clin Chem 2003;49:815–8.10.1373/49.5.815Suche in Google Scholar PubMed

6. Kasper CK, Buzin CH. Mosaics and haemophilia. Haemophilia 2009;15:1181–6.10.1111/j.1365-2516.2009.02003.xSuche in Google Scholar PubMed

7. Tagariello G, Belvini D, Salviato R, Are A, De Biasi E, Goodeve A, et al. Experience of a single Italian center in genetic counseling for hemophilia: from linkage analysis to molecular diagnosis. Haematologica 2000;85:525–9.Suche in Google Scholar PubMed

8. Kulkarni R, Lusher J. Perinatal management of neonates with haemophilia. Br J Haematol 2001;112:264–74.10.1046/j.1365-2141.2001.02362.xSuche in Google Scholar PubMed

9. Maruotti GM, Frisso G, Calcagno G, Fortunato G, Castaldo G, Martinelli P, et al. Prenatal diagnosis of inherited diseases: the 20 years’ experience of an Italian Regional Reference Centre. Clin Chem Lab Med 2013;51:2211–7.10.1515/cclm-2013-0194Suche in Google Scholar PubMed

10. Sanna V, Zarrilli F, Nardiello P, D’Argenio V, Rocino A, Coppola A. Mutational spectrum of F8 gene and prothrombotic gene variants in haemophilia A patients from Southern Italy. Haemophilia 2008;14:796–803.10.1111/j.1365-2516.2008.01705.xhttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000257794400017&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f3Suche in Google Scholar PubMed

11. Ljung R, Lindgren AC, Petrini P, Tengborn L. Normal vaginal delivery is recommended for haemophilia carrier gravidae. Acta Paediatr 1994;83:609–11.10.1111/j.1651-2227.1994.tb13090.xSuche in Google Scholar PubMed

12. Klinge J, Auberger K, Auerswald G, Brackmann HH, Mauz-Korholz C, Kreuz W. Prevalence and outcome of intracranial haemorrhage in haemophiliacs – a survey of the paediatric group of the German Society of Thrombosis and Haemostasis (GTH). Eur J Pediatr 1999;158:162–5.10.1007/PL00014346Suche in Google Scholar PubMed

13. Kenet G, Chan AK, Soucie JM, Kulkarni R. Bleeding disorders in neonates. Haemophilia 2010;16:168–74.10.1111/j.1365-2516.2010.02316.xSuche in Google Scholar PubMed

14. Chi C, Lee CA, Shiltagh N, Khan A, Pollard D, Kadir RA. Pregnancy in carriers of haemophilia. Haemophilia 2008;14: 56–64.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000251860900009&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f3Suche in Google Scholar PubMed

15. Peyvandi F, Bidlingmaier C, Garagiola I. Management of pregnancy and delivery in women with inherited bleeding disorders. Semin Fetal Neonatal Med 2011;16:311–7.10.1016/j.siny.2011.07.006http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000296545500005&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f3Suche in Google Scholar PubMed

16. Karimi M, Peyvandi F, Siboni S, Ardeshiri R, Gringeri A, Mannucci PM. Comparison of attitudes towards prenatal diagnosis and termination of pregnancy for haemophilia in Iran and Italy. Haemophilia 2004;10:367–9.10.1111/j.1365-2516.2004.00927.xSuche in Google Scholar PubMed

17. Balak DM, Gouw SC, Plug I, Maser-Bunschoten EP, Vriends HJ, Van Diemen-Homan JE, et al. Prenatal diagnosis for haemophilia: a national survey among female carriera in the Netherlands. Haemophilia 2012;18:584–92.10.1111/j.1365-2516.2011.02742.xSuche in Google Scholar PubMed

18. Tomaiuolo R, Nardiello P, Martinelli P, Sacchetti L, Salvatore F, Castaldo G. Prenatal diagnosis of cystic fibrosis: an experience of 181 cases. Clin Chem Lab Med 2013;51:2227–32.10.1515/cclm-2013-0200Suche in Google Scholar PubMed

19. Esposito G, Ruggiero R, Savarese M, Savarese G, Tremolaterra MR, Salvatore F, et al. Prenatal molecular diagnosis of inherited neuromuscular diseases: Duchenne/Becker muscular dystrophy, myotonic dystrophy type 1 and spinal muscular atrophy. Clin Chem Lab Med 2013;51:2239–45.10.1515/cclm-2013-0209Suche in Google Scholar PubMed

20. Grosso M, Puzone S, Storino MR, Sessa R, Izzo P. Prenatal diagnosis of hemoglobinopathies: our experience on 523 cases. Clin Chem Lab Med 2013;51:2219–25.10.1515/cclm-2013-0195Suche in Google Scholar PubMed

21. Ljiung RC. Prenatal diagnosis of haemophilia. Haemophilia 1999;5:84–7.10.1046/j.1365-2516.1999.00295.xSuche in Google Scholar PubMed

22. Margaglione M, Castaman GC, Morfini M, Rocino A, Santagostino E, Tagariello G, et al. The Italian AICE-Genetics Hemophilia A database: results and correlation with clinical phenotype. Haematologica 2008;93:722–8.10.3324/haematol.12427http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000255443600012&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f3Suche in Google Scholar PubMed

Received: 2012-12-19
Accepted: 2013-03-08
Published Online: 2013-07-16
Published in Print: 2013-12-01

©2013 by Walter de Gruyter Berlin Boston

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https://doi.org/10.1515/cclm-2013-0205
Schlagwörter für diesen Artikel
amniocentesis; chorionic villi; F8C; F9; haemophilia; prenatal diagnosis

Artikel in diesem Heft

  1. Letters to the Editor
  2. The addition of MESNA in vitro prolongs prothrombin time similar to N-acetyl cysteine
  3. Detection of unknown β-thalassemia cases from atypical HbA1c chromatograms
  4. Analytical study of a new turbidimetric assay for urinary neutrophil gelatinase-associated lipocalin (NGAL) determination
  5. The rare bipolar-contracted red cell significance and correlation with red cell volume
  6. Howell-Jolly body interference in reticulocyte counts
  7. PBMC expressed adiponectin mRNA is predictive of survival in patients with gastric cancer
  8. Comparison study of two commercially available methods for the determination of infliximab, adalimumab, etanercept and anti-drug antibody levels
  9. Development and validation of a rapid and reliable high-performance liquid chromatography method for methadone quantification in human plasma and saliva
  10. Reply to Ruiz-Argüello et al.: Comparison study of two commercially available methods for the determination of infliximab, adalimumab, etanercept and anti-drug antibody levels
  11. Still more discussion on the journal impact factor
  12. The order of draw, myth or science
  13. Masthead
  14. Masthead
  15. Editorial
  16. Multidisciplinarity and interdisciplinarity at work: the prenatal diagnosis
  17. Research Articles
  18. Prenatal diagnosis of inherited diseases: 20 years’ experience of an Italian Regional Reference Centre
  19. Prenatal diagnosis of haemoglobinopathies: our experience of 523 cases
  20. Prenatal diagnosis of cystic fibrosis: an experience of 181 cases
  21. Prenatal diagnosis of haemophilia: our experience of 44 cases
  22. Prenatal molecular diagnosis of inherited neuromuscular diseases: Duchenne/Becker muscular dystrophy, myotonic dystrophy type 1 and spinal muscular atrophy
  23. Editorials
  24. Journal impact factor: the debate continues
  25. Estimation of uncertainty in measurements in the clinical laboratory
  26. Review
  27. Searching for genes involved in hypertension development in special populations: children and pre-eclamptic women. Where are we standing now?
  28. Opinion Paper
  29. More discussion on journal impact factor
  30. General Clinical Chemistry and Laboratory Medicine
  31. Category-specific uncertainty modeling in clinical laboratory measurement processes
  32. The order of draw: myth or science?
  33. Planned variation in preanalytical conditions to evaluate biospecimen stability in the National Children’s Study (NCS)
  34. Longitudinal evaluation of thyroid autoimmunity and function in pregnant Korean women
  35. Evaluation of the N Latex free light chain assay in the diagnosis and monitoring of AL amyloidosis
  36. Identification of an important potential confound in CSF AD studies: aliquot volume
  37. Cancer Diagnostics
  38. Double heterozygosity in the BRCA1 and BRCA2 genes in Italian family
  39. Quantification of EGFR autoantibodies in the amplification phenomenon of HER2 in breast cancer
  40. Diabetes
  41. SAA1 genetic polymorphisms are associated with plasma glucose concentration in non-diabetic subjects
  42. Acknowledgment
  43. Acknowledgment
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