Clinical and Experimental Reproductive Medicine

  • 제40권1호
  • /
  • Pages.42-46
  • /
  • 2013
  • /
  • 2233-8233(pISSN)
  • /
  • 2233-8241(eISSN)
대한생식의학회 (The Korean Society for Reproductive Medicine)
권호 표지
DOI QR코드

DOI QR Code

Successful birth with preimplantation genetic diagnosis using single-cell allele-specific PCR and sequencing in a woman with hypochondroplasia due to FGFR3 mutation (c.1620C>A, p.N540K)

  • Park, Kyung Eui (Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Kim, Sung Ah (Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Kang, Moon Joo (Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Kim, Hee Sun (Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Cho, Sung Im (Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Yoo, Kyoung Won (Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Kim, So Yeon (Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Lee, Hye Jun (Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Oh, Sun Kyung (Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Seong, Moon-Woo (Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Ku, Seung-Yup (Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Jun, Jong Kwan (Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Park, Sung Sup (Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Choi, Young Min (Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Moon, Shin Yong (Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul National University College of Medicine)
  • 투고 : 2012.11.23
  • 심사 : 2013.02.14
  • 발행 : 2013.03.31
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Hypochondroplasia (HCH) is an autosomal dominant inherited skeletal dysplasia, usually caused by a heterozygous mutation in the fibroblast growth factor receptor 3 gene (FGFR3). A 27-year-old HCH woman with a history of two consecutive abortions of HCH-affected fetuses visited our clinic for preimplantation genetic diagnosis (PGD). We confirmed the mutation in the proband (FGFR3:c.1620C>A, p.N540K), and established a nested allele-specific PCR and sequence analysis for PGD using single lymphocyte cells. We performed this molecular genetic analysis to detect the presence of mutation among 20 blastomeres from 18 different embryos, and selected 9 embryos with the wild-type sequence (FGFR3:c.1620C). A successful pregnancy was achieved through a frozen-thawed cycle and resulted in the full-term birth of a normal neonate. To the best of our knowledge, this is the first report of a successful pregnancy and birth using single-cell allele-specific PCR and sequencing for PGD in an HCH patient.

키워드

참고문헌

  1. Goossens V, Traeger-Synodinos J, Coonen E, De Rycke M, Moutou C, Pehlivan T, et al. ESHRE PGD Consortium data collection XI: cycles from January to December 2008 with pregnancy followup to October 2009. Hum Reprod 2012;27:1887-911. https://doi.org/10.1093/humrep/des106
  2. Findlay I, Ray P, Quirke P, Rutherford A, Lilford R. Allelic drop-out and preferential amplification in single cells and human blastomeres: implications for preimplantation diagnosis of sex and cystic fibrosis. Hum Reprod 1995;10:1609-18. https://doi.org/10.1093/HUMREP/10.6.1609
  3. Wells D, Sherlock JK. Strategies for preimplantation genetic diagnosis of single gene disorders by DNA amplification. Prenat Diagn 1998;18:1389-401. https://doi.org/10.1002/(SICI)1097-0223(199812)18:13<1389::AID-PD498>3.0.CO;2-6
  4. Hall BD, Spranger J. Hypochondroplasia: clinical and radiological aspects in 39 cases. Radiology 1979;133:95-100. https://doi.org/10.1148/133.1.95
  5. Keegan K, Johnson DE, Williams LT, Hayman MJ. Characterization of the FGFR-3 gene and its gene product. Ann N Y Acad Sci 1991; 638:400-2. https://doi.org/10.1111/j.1749-6632.1991.tb49052.x
  6. Trujillo-Tiebas MJ, Fenollar-Cortes M, Lorda-Sanchez I, Diaz-Recasens J, Carrillo Redondo A, Ramos-Corrales C, et al. Prenatal diagnosis of skeletal dysplasia due to FGFR3 gene mutations: a 9-year experience: prenatal diagnosis in FGFR3 gene. J Assist Reprod Genet 2009;26:455-60. https://doi.org/10.1007/s10815-009-9339-1
  7. Vajo Z, Francomano CA, Wilkin DJ. The molecular and genetic basis of fibroblast growth factor receptor 3 disorders: the achondroplasia family of skeletal dysplasias, Muenke craniosynostosis, and Crouzon syndrome with acanthosis nigricans. Endocr Rev 2000;21:23-39.
  8. Stenson PD, Ball EV, Mort M, Phillips AD, Shiel JA, Thomas NS, et al. Human Gene Mutation Database (HGMD): 2003 update. Hum Mutat 2003;21:577-81. https://doi.org/10.1002/humu.10212
  9. Cui XF, Li HH, Goradia TM, Lange K, Kazazian HH Jr, Galas D, et al. Single-sperm typing: determination of genetic distance between the G gamma-globin and parathyroid hormone loci by using the polymerase chain reaction and allele-specific oligomers. Proc Natl Acad Sci U S A 1989;86:9389-93. https://doi.org/10.1073/pnas.86.23.9389
  10. Alberola TM, Bautista-Llacer R, Fernandez E, Vendrell X, Perez- Alonso M. Preimplantation genetic diagnosis of P450 oxidoreductase deficiency and Huntington Disease using three different molecular approaches simultaneously. J Assist Reprod Genet 2009;26:263-71. https://doi.org/10.1007/s10815-009-9327-5
  11. Altarescu G, Renbaum P, Brooks PB, Margalioth EJ, Ben Chetrit A, Munter G, et al. Successful polar body-based preimplantation genetic diagnosis for achondroplasia. Reprod Biomed Online 2008;16:276-82. https://doi.org/10.1016/S1472-6483(10)60586-X
  12. Moutou C, Rongieres C, Bettahar-Lebugle K, Gardes N, Philippe C, Viville S. Preimplantation genetic diagnosis for achondroplasia: genetics and gynaecological limits and difficulties. Hum Reprod 2003;18:509-14. https://doi.org/10.1093/humrep/deg123
  13. Hatzaki A, Sifakis S, Apostolopoulou D, Bouzarelou D, Konstantinidou A, Kappou D, et al. FGFR3 related skeletal dysplasias diagnosed prenatally by ultrasonography and molecular analysis: presentation of 17 cases. Am J Med Genet A 2011;155A:2426-35.
  14. Karadimas C, Sifakis S, Valsamopoulos P, Makatsoris C, Velissariou V, Nasioulas G, et al. Prenatal diagnosis of hypochondroplasia: report of two cases. Am J Med Genet A 2006;140:998-1003.
  15. Bellus GA, Spector EB, Speiser PW, Weaver CA, Garber AT, Bryke CR, et al. Distinct missense mutations of the FGFR3 lys650 codon modulate receptor kinase activation and the severity of the skeletal dysplasia phenotype. Am J Hum Genet 2000;67:1411-21. https://doi.org/10.1086/316892
  16. Grigelioniene G, Eklof O, Laurencikas E, Ollars B, Hertel NT, Dumanski JP, et al. Asn540Lys mutation in fibroblast growth factor receptor 3 and phenotype in hypochondroplasia. Acta Paediatr 2000;89:1072-6. https://doi.org/10.1111/j.1651-2227.2000.tb03353.x
  17. Mortier G, Nuytinck L, Craen M, Renard JP, Leroy JG, de Paepe A. Clinical and radiographic features of a family with hypochondroplasia owing to a novel Asn540Ser mutation in the fibroblast growth factor receptor 3 gene. J Med Genet 2000;37:220-4. https://doi.org/10.1136/jmg.37.3.220
  18. Prinster C, Carrera P, Del Maschio M, Weber G, Maghnie M, Vigone MC, et al. Comparison of clinical-radiological and molecular findings in hypochondroplasia. Am J Med Genet 1998;75:109-12. https://doi.org/10.1002/(SICI)1096-8628(19980106)75:1<109::AID-AJMG22>3.0.CO;2-P
  19. Winterpacht A, Hilbert K, Stelzer C, Schweikardt T, Decker H, Segerer H, et al. A novel mutation in FGFR-3 disrupts a putative Nglycosylation site and results in hypochondroplasia. Physiol Genomics 2000;2:9-12. https://doi.org/10.1152/physiolgenomics.2000.2.1.9
  20. Harton GL, De Rycke M, Fiorentino F, Moutou C, SenGupta S, Traeger-Synodinos J, et al. ESHRE PGD consortium best practice guidelines for amplification-based PGD. Hum Reprod 2011;26: 33-40. https://doi.org/10.1093/humrep/deq231