Prenatal detection of cryptic rearrangements by multiplex ligation probe amplification in fetuses with ultrasound abnormalities.
OBJECTIVE
Congenital malformations are a major cause of morbidity and mortality in newborn infants, and genomic imbalances are a significant component of their etiology. The aim of this study was to evaluate the ability of prenatal multiplex ligation probe amplification screening to detect cryptic chromosomal imbalances in fetuses with ultrasound abnormalities of unknown etiology.


METHODS
Multiplex ligation probe amplification was performed with three separate sets of probes: two for subtelomeric regions and one for mental retardation syndrome loci. Sixty-one fetuses with significant ultrasound anomalies and normal karyotype at a minimum of 400-band resolution were tested between January 2007 and January 2009.


RESULTS
We identified four unbalanced rearrangements: one del 18pter/amp 5pter, one del 9pter, one 15q11q13 microdeletion, and one 22q11 microdeletion with atypical presentation. After genetic counseling, two of the pregnancies were terminated.


CONCLUSIONS
Multiplex ligation probe amplification analysis was able to identify clinically significant rearrangements in 6.5% of fetuses with prenatally identified sonographic abnormalities. This prospective study highlights that multiplex ligation probe amplification screening of fetuses with ultrasound abnormalities in the prenatal period is technically feasible and relevant for diagnosis and prognosis.
Goumy
Carole
C
Univ Clermont 1, UFR Médecine, Histologie Embryologie Cytogénétique, Clermont-Ferrand, France. cgoumy@chuclermontferrand.fr
Gouas
Laetitia
L
Pebrel-Richard
Céline
C
Véronèse
Lauren
L
Eymard-Pierre
Eleonore
E
Debost-Legrand
Anne
A
Haoud
Khadidja
K
Tchirkov
Andrei
A
Vago
Philippe
P
D000328:Adult; D002869:Chromosome Aberrations; D005260:Female; D005333:Fetus / Q000002:abnormalities*; D015321:Gene Rearrangement; D005820:Genetic Testing; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D015336:Molecular Probe Techniques; D021141:Nucleic Acid Amplification Techniques; D011247:Pregnancy; D011446:Prospective Studies; D016615:Telomere / Q000235:genetics; D016216:Ultrasonography, Prenatal; D055815:Young Adult