title: Germline mosaicism in Cornelia de Lange syndrome.
abstract: Cornelia de Lange syndrome (CdLS) is a genetic disorder associated with delayed growth, intellectual disability, limb reduction defects, and characteristic facial features. Germline mosaicism has been a described mechanism for CdLS when there are several affected offspring of apparently unaffected parents. Presently, the recurrence risk for CdLS has been estimated to be as high as 1.5%; however, this figure may be an underrepresentation. We report on the molecularly defined germline mosaicism cases from a large CdLS database, representing the first large case series on germline mosaicism in CdLS. Of the 12 families, eight have been previously described; however, four have not. No one specific gene mutation, either in the NIPBL or the SMC1A gene, was associated with an increased risk for germline mosaicism. Suspected or confirmed cases of germline mosaicism in our database range from a conservative 3.4% up to 5.4% of our total cohort. In conclusion, the potential reproductive recurrence risk due to germline mosiacism should be addressed in prenatal counseling for all families who have had a previously affected pregnancy or child with CdLS.
authors.affiliation: Department of Genetics and Center for Human Genetics, University Hospitals of Cleveland, Case Medical Center, Cleveland, Ohio, USA. thomas.slavin@kapiolani.org
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Slavin
authors.forename: Noam
authors.initials: N
authors.lastname: Lazebnik
authors.forename: Dinah M
authors.initials: DM
authors.lastname: Clark
authors.forename: Jaime
authors.initials: J
authors.lastname: Vengoechea
authors.forename: Leslie
authors.initials: L
authors.lastname: Cohen
authors.forename: Maninder
authors.initials: M
authors.lastname: Kaur
authors.forename: Laura
authors.initials: L
authors.lastname: Konczal
authors.forename: Carol A
authors.initials: CA
authors.lastname: Crowe
authors.forename: Jane E
authors.initials: JE
authors.lastname: Corteville
authors.forename: Malgorzata J
authors.initials: MJ
authors.lastname: Nowaczyk
authors.forename: Janice L
authors.initials: JL
authors.lastname: Byrne
authors.forename: Laird G
authors.initials: LG
authors.lastname: Jackson
authors.forename: Ian D
authors.initials: ID
authors.lastname: Krantz
mesh_terms: D018797:Cell Cycle Proteins; D003635:De Lange Syndrome / Q000235:genetics*; D005091:Exons; D005190:Family; D005260:Female; D006801:Humans; D008297:Male; D009030:Mosaicism; D009154:Mutation; D010375:Pedigree; D011506:Proteins / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; C487465:NIPBL protein, human; D011506:Proteins