Computational Prediction of Position Effects of Apparently Balanced Human Chromosomal Rearrangements.

Interpretation of variants of uncertain significance, especially chromosomal rearrangements in non-coding regions of the human genome, remains one of the biggest challenges in modern molecular diagnosis. To improve our understanding and interpretation of such variants, we used high-resolution three-dimensional chromosomal structural data and transcriptional regulatory information to predict position effects and their association with pathogenic phenotypes in 17 subjects with apparently balanced chromosomal abnormalities. We found that the rearrangements predict disruption of long-range chromatin interactions between several enhancers and genes whose annotated clinical features are strongly associated with the subjects' phenotypes.

Vitamin B12 Deficiency in Infancy: The Case for Screening.

The classic principles put forth by Wilson and Jungner are often applied to determine the suitability of a condition for universal newborn screening. The three cases described here portray the harmful effects of vitamin B12 deficiency in infancy. The challenges and opportunities of early recognition and treatment are highlighted.

Suitability of rapid aneuploidy detection for prenatal diagnosis.

Objective: To determine the suitability of replacing full karyotype analysis with molecular genetic rapid aneuploidy detection (RAD) methods, in particular quantitative fluorescence polymerase chain reaction (QF-PCR), for prenatal diagnosis in amniotic fluid samples obtained by amniocentesis.

Methods: We reviewed all fetal karyotypes done at our centre between August 29, 2000, and February 28, 2006. Outcome measures included (1) the proportion of prenatal samples with abnormal karyotypes that would not have been detected by RAD, as a whole and for each indication, and (2) pregnancy outcome for each chromosome abnormality that was predicted to be clinically significant or of uncertain significance and would not have been detected by RAD.