Detection of cryptic subtelomeric imbalances in fetuses with ultrasound abnormalities.
It is known from postnatal diagnosis that imbalances of the subtelomeric regions contribute significantly to idiopathic mental retardation. Consequently, subtelomere screening has been incorporated into the recommendations for the evaluation of individuals with unexplained mental retardation and a normal karyotype. Previous studies suggested that for fetuses with ultrasound abnormalities and a normal karyotype, additional screening for submicroscopic imbalances can be relevant for diagnosis and prognosis. In the present paper, we report the detection of such (subtelomeric) imbalances in three fetuses. Prenatally, the three fetuses presented with ultrasound abnormalities highly suspected of a chromosomal aberration. In two of the fetuses, routine karyotyping showed no aberrations but with MLPA or FISH a small subtelomeric imbalance, that could explain the anomalies, was detected. In the third fetus, a chromosomal abnormality was detected with routine cytogenetic analysis (del(X)(p22.1)), but this abnormality could not explain the ultrasound observations and only with subtelomere screening by MLPA a causative chromosomal aberration was detected. As the three fetuses were already prenatally suspected of a chromosomal aberration, this underlines the potential relevance of subtelomere screening in such fetuses, leading to better clinical diagnosis, prognosis and care. Furthermore, when using MLPA, the analysis can be extended to other regions of known clinical importance.
Faas
Brigitte H W
BH
Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. b.faas@antrg.umcn.nl
Nillesen
Willy
W
Vermeer
Sascha
S
Weghuis
Daniel Olde
DO
de Leeuw
Nicole
N
Smits
Arie P T
AP
van Ravenswaaij-Arts
Conny M A
CM
D002869:Chromosome Aberrations; D041321:Chromosomes, Human, X; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007231:Infant, Newborn; D007621:Karyotyping; D016615:Telomere; D016216:Ultrasonography, Prenatal