Articles| Volume 2, ISSUE 1, P17-19, 2001

Preimplantation diagnosis for long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency

      This paper is only available as a PDF. To read, Please Download here.


      Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency is a fatal autosomal recessive metabolic disorder, presenting during infancy. Preimplantation genetic diagnosis (PGD) provides an option for establishing an unaffected pregnancy, avoiding the risk for termination of pregnancy following prenatal diagnosis. The method for pre-selection of mutation-free oocytes for LCHAD deficiency was developed by testing the first and second polar body removed from oocytes by micromanipulation techniques in the framework of in-vitro fertilization. To avoid misdiagnosis, testing was done using hemi-nested polymerase chain reaction (PCR), with outer primers designed to lie outside the pseudogene, eliminating false priming. Four of 12 tested oocytes were predicted to be unaffected, based on the heterozygous first and mutant second polar body. The embryos resulting from these mutation-free oocytes were replaced, yielding a singleton clinical pregnancy and birth of a healthy child following confirmation by prenatal diagnosis.



        • Ding JH
        • Yang BZ
        • Nada MA
        • Roe CR
        Improved detection of the G1528C mutation in LCHAD deficiency.
        Biochemical and Molecular Medicine. 1996; 58: 46-51
        • Ijlst L
        • Ruiter JP
        • Hoovers JM
        • et al.
        Common missense mutation G1528C in long-chain 3-hydroxyacil-CoA dehydrogenase deficiency. Characterization and expression of the mutant protein, mutation analysis on genomic DNA and chromosomal localization of the mitichondrial trifunctional protein alpha subunit gene.
        Journal of Clinical Investigation. 1999; 98: 1028-1033
        • International Working Group on Preimplantation Genetics
        10th anniversary of preimplantation genetic diagnosis. Report of the 10th annual meeting of international working group on preimplantation genetics, in conjunction with the 3rd International Symposium on Preimplantation Genetics, Bologna 22-23 June 2000.
        Journal of Assisted Reproduction and Genetics. 2001; 18: 66-72
        • International Working Group on Preimplantation Genetics
        Preimplantation diagnosis: an alternative to prenatal diagnosis of genetic and chromosomal disorders. Report of the 8th annual meeting international working group on preimplantation genetics, in association with the 9th International Conference on Prenatal Diagnosis and Therapy, Los Angeles, 7 June, 1998.
        Journal of Assisted Reproduction and Genetics. 1999; 16: 161-164
        • Rechitsky S
        • Strom C
        • Verlinsky O
        • et al.
        Accuracy of preimplantation diagnosis of single-gene disorders by polar body analysis of oocytes.
        Journal of Assisted Reproduction and Genetics. 1999; 16: 192-198
        • Sims HF
        • Brackett JC
        • Powell CK
        • et al.
        The molecular basis of pediatric long chain 3-hydroxyacyl-CoA dehydrogenase deficiency associated with maternal acute fatty liver of pregnancy.
        Proceedings of the National Academy of Sciences of the United States of America. 1995; 92: 841-845
        • Tyni T
        • Pihko H
        Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency.
        Acta Paediatrica. 1999; 88: 237-245
        • Verlinsky Y
        • Kuliev A.
        Atlas of Preimplantation Genetic Diagnosis. Parthenon, New York and London2000
        • Verlinsky Y
        • Rechitsky S
        • Cieslak J
        • et al.
        Preimplantation diagnosis of single gene disorders by two-step oocyte analysis using first and second polar body.
        Biochemical and Molecular Medicine. 1997; 62: 182-187
        • Verlinsky Y
        • Rechitsky S
        • Verlinsky O
        • et al.
        Prepregnancy testing for single-gene disorders by polar body analysis.
        Genetic Testing. 1999; 3: 185-190
        • Verlinsky Y
        • Rechitsky S
        • Verlinsky O
        • et al.
        Preimplantation diagnosis for ornithine transcarbamylase deficiency.
        Reproductive BioMedicine Online. 2000; 1: 45-47


      Dr. Yury Verlinsky is a graduate, postgraduate and PhD of Kharkov University of the former USSR. His research interests include cytogenetics, embryology and prenatal and preimplantation genetics. He introduced polar body testing for preimplantation genetic diagnosis and developed the methods for karyotyping second polar body and individual blastomeres. He has published over 100 papers, as well as three books on preimplantation genetics.