Clinical utility of chromosomal microarray analysis in invasive prenatal diagnosis

Lluís Armengol, Julián Nevado, Clara Serra-Juhé, Alberto Plaja, Carmen Mediano, Fe Amalia García-Santiago, Manel García-Aragonés, Olaya Villa, Elena Mansilla, Cristina Preciado, Luis Fernández, María Ángeles Mori, Lidia García-Pérez, Pablo Daniel Lapunzina, Luis Perez-Jurado

Research output: Contribution to journalArticle

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Abstract

Novel methodologies for detection of chromosomal abnormalities have been made available in the recent years but their clinical utility in prenatal settings is still unknown. We have conducted a comparative study of currently available methodologies for detection of chromosomal abnormalities after invasive prenatal sampling.Amulticentric collection of a 1-year series of fetal samples with indication for prenatal invasive sampling was simultaneously evaluated using three screening methodologies: (1) karyotype and quantitative fluorescent polymerase chain reaction (QF-PCR), (2) two panels of multiplex ligation-dependent probe amplification (MLPA), and (3) chromosomal microarray-based analysis (CMA) with a targeted BAC microarray. A total of 900 pregnantwomen provided informed consent to participate (94% acceptance rate). Technical performance was excellent for karyotype, QF-PCR, and CMA (∼1% failure rate), but relatively poor for MLPA (10% failure). Mean turn-around time (TAT) was 7 days forCMA orMLPA, 25 for karyotype, and two for QF-PCR, with similar combined costs for the different approaches. A total of 57 clinically significant chromosomal aberrations were found (6.3%), with CMA yielding the highest detection rate (32% above other methods). The identification of variants of uncertain clinical significance by CMA (17, 1.9%) tripled that of karyotype and MLPA, but most alterations could be classified as likely benign after proving they all were inherited. High acceptability, significantly higher detection rate and lower TAT, could justify the higher cost of CMAand favor targeted CMA as the best method for detection of chromosomal abnormalities in at-risk pregnancies after invasive prenatal sampling.

LanguageEnglish
Pages513-523
Number of pages11
JournalHuman Genetics
Volume131
Issue number3
DOIs
Publication statusPublished - 1 Mar 2012
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Armengol, L., Nevado, J., Serra-Juhé, C., Plaja, A., Mediano, C., García-Santiago, F. A., ... Perez-Jurado, L. (2012). Clinical utility of chromosomal microarray analysis in invasive prenatal diagnosis. Human Genetics, 131(3), 513-523. https://doi.org/10.1007/s00439-011-1095-5
Armengol, Lluís ; Nevado, Julián ; Serra-Juhé, Clara ; Plaja, Alberto ; Mediano, Carmen ; García-Santiago, Fe Amalia ; García-Aragonés, Manel ; Villa, Olaya ; Mansilla, Elena ; Preciado, Cristina ; Fernández, Luis ; Mori, María Ángeles ; García-Pérez, Lidia ; Lapunzina, Pablo Daniel ; Perez-Jurado, Luis. / Clinical utility of chromosomal microarray analysis in invasive prenatal diagnosis. In: Human Genetics. 2012 ; Vol. 131, No. 3. pp. 513-523.
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Armengol, L, Nevado, J, Serra-Juhé, C, Plaja, A, Mediano, C, García-Santiago, FA, García-Aragonés, M, Villa, O, Mansilla, E, Preciado, C, Fernández, L, Mori, MÁ, García-Pérez, L, Lapunzina, PD & Perez-Jurado, L 2012, 'Clinical utility of chromosomal microarray analysis in invasive prenatal diagnosis', Human Genetics, vol. 131, no. 3, pp. 513-523. https://doi.org/10.1007/s00439-011-1095-5

Clinical utility of chromosomal microarray analysis in invasive prenatal diagnosis. / Armengol, Lluís; Nevado, Julián; Serra-Juhé, Clara; Plaja, Alberto; Mediano, Carmen; García-Santiago, Fe Amalia; García-Aragonés, Manel; Villa, Olaya; Mansilla, Elena; Preciado, Cristina; Fernández, Luis; Mori, María Ángeles; García-Pérez, Lidia; Lapunzina, Pablo Daniel; Perez-Jurado, Luis.

In: Human Genetics, Vol. 131, No. 3, 01.03.2012, p. 513-523.

Research output: Contribution to journalArticle

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AU - Serra-Juhé, Clara

AU - Plaja, Alberto

AU - Mediano, Carmen

AU - García-Santiago, Fe Amalia

AU - García-Aragonés, Manel

AU - Villa, Olaya

AU - Mansilla, Elena

AU - Preciado, Cristina

AU - Fernández, Luis

AU - Mori, María Ángeles

AU - García-Pérez, Lidia

AU - Lapunzina, Pablo Daniel

AU - Perez-Jurado, Luis

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Armengol L, Nevado J, Serra-Juhé C, Plaja A, Mediano C, García-Santiago FA et al. Clinical utility of chromosomal microarray analysis in invasive prenatal diagnosis. Human Genetics. 2012 Mar 1;131(3):513-523. https://doi.org/10.1007/s00439-011-1095-5