title: Large genomic rearrangements in NIPBL are infrequent in Cornelia de Lange syndrome.
abstract: Cornelia de Lange Syndrome (CdLS) is a multiple congenital anomaly syndrome characterized by a distinctive facial appearance, malformations of the upper limbs, and delay in growth and development. Mutations in NIPBL are associated with CdLS in 27-56% of cases and have been reported as point mutations, small insertions and deletions in coding regions, regulatory regions and at splice junctions. All previous studies used PCR-based exon-scanning methodologies that do not allow detection of large genomic rearrangements. We studied the relative copy number of NIPBL exons in a series of 50 CdLS probands, negative for NIPBL mutations, by multiplex ligation-dependent probe amplification (MLPA). In a single patient, we found a 5.2 kb deletion encompassing exons 41-42 of NIPBL. Our studies indicate that large NIPBL rearrangements do occur in CdLS but are likely to be infrequent events.
authors.affiliation: Department of Clinical Genetics, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. Z.A.Bhuiyan@amc.uva.nl
authors.forename: Zahurul A
authors.initials: ZA
authors.lastname: Bhuiyan
authors.forename: Helen
authors.initials: H
authors.lastname: Stewart
authors.forename: Egbert J
authors.initials: EJ
authors.lastname: Redeker
authors.forename: Marcel M A M
authors.initials: MM
authors.lastname: Mannens
authors.forename: Raoul C M
authors.initials: RC
authors.lastname: Hennekam
mesh_terms: D000293:Adolescent; D000328:Adult; D018797:Cell Cycle Proteins; D002648:Child; D002675:Child, Preschool; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D015331:Cohort Studies; D004252:DNA Mutational Analysis / Q000379:methods; D003635:De Lange Syndrome / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D015321:Gene Rearrangement; D015894:Genome, Human; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D021141:Nucleic Acid Amplification Techniques / Q000379:methods; D010375:Pedigree; D010641:Phenotype; D011506:Proteins / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; C487465:NIPBL protein, human; D011506:Proteins