Document Detail

First specific preimplantation genetic diagnosis for ornithine transcarbamylase deficiency.
MedLine Citation:
PMID:  11180228     Owner:  NLM     Status:  MEDLINE    
Ornithine transcarbamylase (OTC) deficiency is an X-linked dominant metabolic disorder with partial penetrance in heterozygous females. Affected boys usually die from hyperammonemia in the first few days of life, while clinical expression in carrier females ranges from no symptoms to neonatal death. A young couple whose boy had died of OTC deficiency in the neonatal period was referred to our genetic department for their subsequent pregnancy. The fetus was found to be affected, and after genetic counseling the pregnancy was terminated. Prenatal diagnosis of the third pregnancy identified a heterozygous female, who died after a normal birth at age 11 days from hyperammonemia. After this, the couple asked for preimplantation genetic diagnosis (PGD). We have developed a duplex nested PCR assay allowing the amplification of both the mutation and an informative restriction fragment length polymorphism (RFLP) located in the 3' end of the OTC gene. After nested amplification, allele identification was carried out for both loci by double restriction digestion and electrophoresis gel analysis. The co-amplification of both loci provided a means of detecting potential allele dropout or incomplete digestion. Two PGD cycles were carried out, a total of 14 embryos were analysed and a diagnosis could be obtained in 13/14 embryos. There were four unaffected male embryos, four heterozygous females and four unaffected females; the final embryo was an affected one of undetermined gender. In both cycles, three unaffected embryos could be transferred early on Day 4 post-insemination. The second cycle resulted in the birth of a baby boy devoid of the OTC mutation. This constitutes the first birth following PGD carried out by a French team.
P F Ray; N Gigarel; J P Bonnefont; T Attié; S Hamamah; N Frydman; M Vekemans; R Frydman; A Munnich
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Publication Detail:
Type:  Case Reports; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Prenatal diagnosis     Volume:  20     ISSN:  0197-3851     ISO Abbreviation:  Prenat. Diagn.     Publication Date:  2000 Dec 
Date Detail:
Created Date:  2001-02-22     Completed Date:  2001-04-12     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8106540     Medline TA:  Prenat Diagn     Country:  England    
Other Details:
Languages:  eng     Pagination:  1048-54     Citation Subset:  IM    
Copyright Information:
Copyright 2000 John Wiley & Sons, Ltd.
Département de génétique et unité U393, Hôpital Necker Enfants Malades, 75743 Paris Cedex 15, France.
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MeSH Terms
Base Sequence
DNA Mutational Analysis
Embryo Transfer
Embryo, Mammalian
Hyperammonemia / etiology
Linkage (Genetics)
Ornithine Carbamoyltransferase / genetics*
Ornithine Carbamoyltransferase Deficiency Disease*
Polymerase Chain Reaction
Polymorphism, Restriction Fragment Length
Preimplantation Diagnosis*
Sperm Injections, Intracytoplasmic
X Chromosome
Reg. No./Substance:
EC Carbamoyltransferase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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