Prenatal sex determination in suspicious cases of X-linked recessive diseases by the amelogenin gene

Document Type : Original Article


1 Molecular Medicine Department, Pasteur Institute of Iran, Tehran, Iran

2 Department of Microbiology, Islamic Azad University, Shahr-e- Qods Branch, Tehran, Iran

3 Medical Biotechnology Department, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran

4 Department of Pharmacology, Tehran Medical Science Branch, Islamic Azad University, Tehran, Iran


Objective(s):To determine the fetal discernment in suspected cases of sex linked recessive disease in the first trimester of pregnancy.
Materials and Methods: After collection of 100 Chorionic Villi samples, the DNAs were extracted and baby gender was determined. Meanwhile, after increasing the sensitivity, the system was able to detect the sex of each cell which was obtained by biopsy.
Results: Early fetal gender of 100 Chorionic Villi samples were assessed by PCR. After increasing sensitivity of the assay, the sexes in 13 fetuses that were in different cellular stages were detected. Morover, sexes were detected in two unfertilized and one fertilized ovum but without any division.
Conclusion: Sex detection of fetus before delivery in the first trimester of pregnancy, will prevent babies with abnormalities being born. It can also be used in detection of recessive sex related diseases in In Vitro Fertilization cases for sex detection and to transfer female fetus to the mother. Our optimized molecular detection system was designed on the basis of amelogenin gene, which can determine the sex in blood, chorionic villi, and single cell in vitro fertilization with high sensitivity and specificity.


 1. Wells D, Delhanty JDA. Preimplantation genetic medicine: applications for molecular medicine. TRENDA in Molecular Medicine 2001; 7(1): 23-30.
2. Braude P, Pickering S, Flinter F, Ogilvie CM. Preimplantation genetic diagnosis. Nature Review Genetics 2002; 13: 941-953.
3. Wright CF, Wei Y, Higgins JPT, Sagoo Gs. Non-invasive prenatal diagnostic test accuracy for fetal sex using cell-free DNA a review and meta-analysis. BMC Research Notes 2012; 5:476.
4. Impey SLC. Prenatal diagnosis: Type and techniques. Early Human Development 2012; 88: 3–8.
5. Hill M, Barrett AN, White H, Chitty LS. Use of cell free fetal DNA in maternal circulation. Best Practice & Research Clinical Obstetrics and Gynaecology 2012; 26: 639-654.
6. Simpson JL. Invasive procedures for prenatal diagnosis: Any future left. Best Practice & Research Clinical Obstetrics and Gynaecology 2012; 26: 625–638.
7. Tozzo P, Giuliodori A, Corato S, Ponzano E, Rodriguez D, Caenazzo L. Deletion of amelogenin Y-locus in forensics: Literature revision and description of a novel method for sex conformation. Journal of Forensic and Legal Medicine 2013; XXX: 1-5.
8. Nakahori Y, Takenaka O, Nakagome Y. A human X-Y homologous region encodes amelogenin. Genomics 1991; 9 (2): 264–9.
9. Sambrook J, Fritsch EF, Maniatis T. Molecular cloning: a laboratory manual. 3rd ed. Cold Spring Harbor: New York; 2001.
10. Mazza V, Falcinelli C, Percesepe A, Paganelli S, Volpe A, Forabosco A. Non-invasive first trimester fetal gender assignment in pregnancies at risk for X-linked recessive disease. Prenat Diagn 2002; 22: 919-924.
11. Finning KM, Chitty LS. Non-invasive fetal determination: Impact on clinical practice. Seminars in Fetal & Neonatal Medicine 2008; 13: 69-75.
12. Smid M, Lagona F, de Benassuti L, Ferrari A, Ferrari M, Cremonesi L. Evaluation of different approaches for fetal DNA analysis from maternal plasma and nucleated blood cells. Clin Chem 1999; 45: 1570-1572.
13. Hill M, Finning K, Martin P, Hogg J, Meaney C, Norbury G, Daniels G, Chitty LS. Non-invasive prenatal determination of fetal sex: translating research into clinical practice. Clin Genet 2011; 80: 68–75.
14. Tasinato P, Montisci M, te Kronnie G, Basso G. Non-medical applications if non-invasive prenatal diagnosis: Ethical issues. Forensic Science International: Genetics 2011; Supplement Series 3: 554–555.
15. Tungwiwat W, Fucharoen G, Ratanasiri T, Sanchaisuriya K, Fucharoen S. Non-invasive fetal sex determination using a conventional nested PCR analysis of fetal DNA in maternal plasma. Clinica Chimica Acta 2003; 334: 173-177.
16. Van de Velde H, Vos AD, Sermon K, Staessen C, Rycke Md., Van Assche E, Lissens W, Vandervorst M, Van Ranst H, Liebaers I, Van Steirteghem A. Embryo implantation after biopsy of one or two cells from cleavage-stage embryos with a view to preimplantation genetic diagnosis. Prenat Diagn 2000; 20:1030-1037.
17. Handyside AH, Delhanty JDA. Preimplantation genetic diagnosis: strategies and surprises. TIG 1997; 3: 270-275.