title: Spectrum of NIPBL gene mutations in Polish patients with Cornelia de Lange syndrome.
abstract: Cornelia de Lange syndrome (CdLS) is a rare multi-system genetic disorder characterised by growth and developmental delay, distinctive facial dysmorphism, limb malformations and multiple organ defects. The disease is caused by mutations in genes responsible for the formation and regulation of cohesin complex. About half of the cases result from mutations in the NIPBL gene coding delangin, a protein regulating the initialisation of cohesion. To date, approximately 250 point mutations have been identified in more than 300 CdLS patients worldwide. In the present study, conducted on a group of 64 unrelated Polish CdLS patients, 25 various NIPBL sequence variants, including 22 novel point mutations, were detected. Additionally, large genomic deletions on chromosome 5p13 encompassing the NIPBL gene locus were detected in two patients with the most severe CdLS phenotype. Taken together, 42 % of patients were found to have a deleterious alteration affecting the NIPBL gene, by and large private ones (89 %). The review of the types of mutations found so far in Polish patients, their frequency and correlation with the severity of the observed phenotype shows that Polish CdLS cases do not significantly differ from other populations.
authors.affiliation: Department of Biology and Genetics, Medical University of Gdansk, Debinki 1 str., 80211, Gdansk, Poland.
authors.forename: Alina
authors.initials: A
authors.lastname: Kuzniacka
authors.forename: Jolanta
authors.initials: J
authors.lastname: Wierzba
authors.forename: Magdalena
authors.initials: M
authors.lastname: Ratajska
authors.forename: Beata S
authors.initials: BS
authors.lastname: Lipska
authors.forename: Magdalena
authors.initials: M
authors.lastname: Koczkowska
authors.forename: Monika
authors.initials: M
authors.lastname: Malinowska
authors.forename: Janusz
authors.initials: J
authors.lastname: Limon
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D003635:De Lange Syndrome / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D017354:Point Mutation; D011044:Poland; D011506:Proteins / Q000235:genetics*; D017384:Sequence Deletion; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D011506:Proteins; D000097722:Cohesins; C487465:NIPBL protein, human