title: Premature chromatid separation is not a useful diagnostic marker for Cornelia de Lange syndrome.
abstract: Cornelia de Lange syndrome (CdLS) is a rare, multiple congenital anomaly/mental retardation syndrome characterized by clinical variability and caused by mutations in the NIPBL (50-60%), SMC1L1 and SMC3 genes (5%), which encode for proteins involved in sister chromatid cohesion. Almost all of the studies of premature chromatid separation (PCS) in CdLS patients have failed to demonstrate that it is specific to CdLS, thus making its diagnostic use controversial. In order to verify the diagnostic usefulness of PCS screening in CdLS, we analysed metaphase spreads from 29 CdLS patients and 24 controls using a rigorous protocol to induce PCS, and precise criteria to score the affected chromosomes. Following exclusion of significant intra-sample variation we scored under blind conditions 150 spreads from a single preparation of each case and computed the ratio between the number of prematurely separated chromatids and the total number of chromatids. The results indicate the extreme variability of PCS in both cohorts (CdLS: mean 2.8 +/- 2.8%; controls: mean 4.0 +/- 5.4%) and highlight the difficulty of PCS monitoring, especially when selecting the control population. The absence of any difference in the frequency of PCS between the patients and controls, or between patients with different clinical or genetic backgrounds, precludes its potential use as an additional diagnostic tool.
authors.affiliation: Division of Medical Genetics, San Paolo School of Medicine, University of Milan, via A. di Rudinì 8, 20142 Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Castronovo
authors.forename: Cristina
authors.initials: C
authors.lastname: Gervasini
authors.forename: Anna
authors.initials: A
authors.lastname: Cereda
authors.forename: Maura
authors.initials: M
authors.lastname: Masciadri
authors.forename: Donatella
authors.initials: D
authors.lastname: Milani
authors.forename: Silvia
authors.initials: S
authors.lastname: Russo
authors.forename: Angelo
authors.initials: A
authors.lastname: Selicorni
authors.forename: Lidia
authors.initials: L
authors.lastname: Larizza
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002842:Chromatids / Q000235:genetics* / Q000473:pathology; D020090:Chromosome Segregation / Q000235:genetics*; D002877:Chromosomes, Human / Q000235:genetics; D015331:Cohort Studies; D055028:Comparative Genomic Hybridization; D003635:De Lange Syndrome / Q000175:diagnosis / Q000235:genetics*; D005189:False Positive Reactions; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008677:Metaphase; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D012854:Sister Chromatid Exchange / Q000235:genetics*; D055815:Young Adult
chemical_list: D005819:Genetic Markers
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