Abstract
Purpose
Development of an ad hoc protocol for the preimplantion genetic diagnosis of propionic acidemia in a couple carrying the mutations c.737G>T (G246V) and c.1218del14ins12 (ins/del) in the PCCB gene. Propionic acidemia is an autosomal recessive metabolic disorder where the body is unable to process certain parts of proteins and lipids. Symptoms manifest few days after birth and sometimes progress to more serious medical problems, including heart abnormalities, coma and death.
Methods
Four short tandem repeat markers closely linked to the PCCB gene were tested, in order to support the direct mutation detection diagnosis. Multiplex fluorescent heminested polymerase chain reaction followed by fragment analysis and minisequencing was used.
Results
Fourteen single blastomeres from nine embryos were tested and two carrier embryos were transferred, resulting in the birth of two healthy boys.
Conclusions
Preimplantation genetic diagnosis represents a valid reproductive option for couples affected of propionic acidemia, in order to avoid transmission to offspring.
References
Gardner RL, Edwards LG. Control of the sex ratio at full term in the rabbit by transferring sexed blastocysts. Nature. 1968;218:346–9.
Handyside AH, Kontogianni EH, Hardy K, Winston RM. Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplification. Nature. 1990;344:768–70.
Preimplantation Genetic Diagnosis International Society (PGDIS). Guidelines for good practice in PGD: programme requirements and laboratory quality assurance. Reprod Biomed Online. 2008;16:134–47.
Goossens V, Harton G, Moutou C, Traeger-Synodinos J, Van Rij M, Harper JC. ESHRE PGD Consortium data collection IX: cycles from January to December 2006 with pregnancy follow-up to October 2007. Hum Reprod. 2009;24:1786–810.
Ravn K, Chloupkova M, Christensen E, Simonsen H, Kraus JP, Nielsen IM, et al. High incidence of propionic academia in Greenland is due to a prevalent mutation, 1540insCCC, in the gene for the beta-subunit of propionyl CoA carboxylase. Am J Hum Genet. 2000;67:203–6.
Pérez-Cerdá C, Merinero B, Rodríguez-Pombo P, Pérez B, Desviat LR, Muro S, et al. Ugarte M. Potential relationship between genotype and clinical outcome in propionic acidaemia patients. Eur J Hum Genet. 2000;8:187–94.
Yorifuji T, Kawai M, Muroi J, Mamada M, Kurokawa K, Shigematsu Y, et al. Unexpectedly high prevalence of the mild form of propionic acidemia in Japan: presence of a common mutation and possible clinical implications. Hum Genet. 2002;111:161–5.
Schulze A, Lindner M, Kohlmuller D, Olgemöller K, Mayatepek E, Hoffmann GF. Expanded newborn screening for inborn errors of metabolism by electrospray ionization-tandem mass spectrometry: results, outcome, and implications. Pediatrics. 2003;111:1399–406.
Paz Valiñas L, Atienza Merino G. Clinical effectiveness of neonatal screening for inborn errors of metabolismo using tandem mass spectrometry (Sistematic Revision). Madrid: Ministerio de Sanidad y Consumo. Avalia-t. Nº 2006/07.
Richard E, Desviat LR, Pérez B, Pérez-Cerdá C, Ugarte M. Genetic heterogeneity in propionic acidemia patients with alpha-subunit defects. Identification of five novel mutations, one of them causing instability of the protein. Biochim Biophys Acta. 1999;1453:351–8.
ISO 9001. Quality management systems-requirements. Geneva: International Organization for Standarization; 2008.
Vendrell X, Carrero R, Alberola T, Bautista-Llácer R, García-Mengual E, Claramunt R, et al. Quality management system in PGD/PGS: now is the time. J Assist Reprod Genet. 2009;26:197–204.
Cui XF, Li HH, Goradia TM, Kazazian Jr HH, Galas D, Arnheim N. 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 USA. 1989;86:9389–93.
Alberola TM, Bautista-Llácer R, Fernández E, Vendrell X, Pérez-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.
Dionisi-Vici C, Deodato F, Röschinger W, Rhead W, Wilcken BL. ‘Classical’ organic acidurias, propionic aciduria, methylmalonic aciduria and isovaleric aciduria: long-term outcome and effects of expanded newborn screening using tandem mass spectrometry. J Inherit Metab Dis. 2006;29:383–9.
Pérez B, Desviat LR, Rodríguez-Pombo P, Clavero S, Navarrete R, Perez-Cerdá C, et al. Propionic acidemia: identification of twenty-four novel mutations in Europe and North America. Mol Genet Metab. 2003;78:59–67.
Desviat LR, Pérez B, Pérez-Cerdá C, Rodríguez-Pombo P, Clavero S, Ugarte M. Propionic acidemia: mutation update and functional and structural effects of the variant alleles. Mol Genet Metab. 2004;83:28–37.
Thornhill AR, deDie-Smulders CE, Geraedts JP, Harper JC, Harton GL, et al. ESHRE PGD Consortium ‘Best practice guidelines for clinical preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS)’. Hum Reprod. 2005;20:35–48.
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Capsule A description of a PGD cycle for the detection of propionic acidemia, resulting in the birth of two healthy boys.
A couple with a dead son affected of propionic acidemia underwent preimplantation genetic diagnosis to prevent the transmission of this disease to their offspring
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Alberola, T.M., Bautista-Llácer, R., Vendrell, X. et al. Case report: birth of healthy twins after preimplantation genetic diagnosis of propionic acidemia. J Assist Reprod Genet 28, 211–216 (2011). https://doi.org/10.1007/s10815-010-9514-4
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DOI: https://doi.org/10.1007/s10815-010-9514-4