MLPA as a screening method of aneuploidy and unbalanced chromosomal rearrangements in spontaneous miscarriages

Prenat Diagn. 2007 Aug;27(8):765-71. doi: 10.1002/pd.1777.

Abstract

Objective: The present study aims to validate multiplex ligation-dependent probe amplification (MLPA) technique with subtelomeric probe mixes as a screening method to detect aneuploidy and unbalanced terminal chromosomal rearrangements in spontaneous abortions (SAs).

Methods: MLPA with P036B and P070 probe mixes was performed on 221 miscarriage DNA samples between the 5th and 24th week of gestation. Cytogenetic culture was attempted on 178 miscarriages. Karyotyped miscarriages served as controls in this blinded study. Results were confirmed by quantitative fluorescent-PCR (QF-PCR).

Results: Among the karyotyped miscarriages, MLPA was able to detect all the expected aneuploidies, as well as an unbalanced product from a reciprocal translocation, and revealed cryptic deletions and duplications not visible at the 550-band resolution level. In addition, chromosomal anomalies were found in approximately 37% of cases that failed to grow or could not be cultivated. As expected, ploidy changes were not detected. Copy number variation was found for target sequences of P036B (CYFIP1, MRPL41, CAB45) and P070 (DECR2, TNFRSF18) probe mixes.

Conclusions: We propose the use of MLPA with subtelomeric probe mixes as a reliable, rapid and economical first approach to detect aneuploidy and unbalanced terminal chromosomal rearrangements in SAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Spontaneous / genetics*
  • Abortion, Spontaneous / pathology
  • Adult
  • Aneuploidy*
  • Cells, Cultured
  • DNA / analysis
  • DNA / genetics
  • Female
  • Gene Rearrangement / genetics*
  • Genetic Markers
  • Genetic Testing / methods*
  • Humans
  • Karyotyping
  • Nucleic Acid Amplification Techniques / methods*
  • Polymerase Chain Reaction
  • Pregnancy
  • Single-Blind Method

Substances

  • Genetic Markers
  • DNA