Detection of trisomy 21 by quantitative mass spectrometric analysis of single-nucleotide polymorphisms.

with the p.R110X mutation, as was described recently (13). Although p.R110X is one of the few recurrent mutations of this gene, we were unable to find other clinical descriptions of female patients carrying this mutation , and the movement disorder in CLS, although common, is not well studied. No clear hot spot mutations were found, thus highlighting the functional relevance of both protein kinase domains. In patients negative for RSK2 mutations by DHPLC analysis, direct sequencing of the entire gene failed to detect any variations. Moreover, no false-positive results were reported, each abnormal chromatogram containing 1 mutation or polymorphism. The detection rate in our patients was 7 of 16 (44%), and despite the small number of patients, we believe that it represents a significant increase in the sensitivity of RSK2 mutational screening compared with the recent literature. Among patients who were negative on RSK2 mutation analysis, only 2 exhibited a typical CLS phenotype. As suggested previously (14), genetic heterogeneity or defects in regions not investigated by this assay can account for the failure in detecting RSK2 mutations in those patients. Including the time to set up the PCR reaction and to perform the DHPLC, analysis time was ϳ6 h to screen the entire coding region of the RSK2 gene, thus providing a high-throughput alternative to single-strand conforma-tional polymorphism– based analysis for molecular pre-screening in CLS patients. We gratefully acknowledge financial support from the Italian Ministry of Health. Mutation analysis of the RSK2 gene in Coffin-Lowry patients: extensive allelic heterogeneity and a high rate of de novo mutations. Expression analysis of RSK gene family members: the RSK2 gene, mutated in Coffin-Lowry syndrome, is prominently expressed in brain structures essential for cognitive function and learning. The p53 protein is a novel substrate of ribosomal S6 kinase 2 and a critical intermediary for ribosomal S6 kinase 2 and histone H3 interaction. et al. Unreported RSK2 missense mutation in two male sibs with an unusually mild form of Coffin-Lowry syndrome. Down syndrome is the most common chromosomal abnormality of live-born babies. Currently, cytogenetic analysis of fetal cells such as full chromosome karyotyping (1) and fluorescence in situ hybridization (2) are the most widely used techniques for prenatal diagnosis of this chromosomal aneuploidy. Recently, however, alternative molecular strategies have been developed. Quantitative fluorescence PCR involves the detection of short tandem repeats on chromosome 21 and is by far the most thoroughly evaluated molecular technique. Additional …