title: Search for genomic imbalances in a cohort of 24 Cornelia de Lange patients negative for mutations in the NIPBL and SMC1L1 genes.
abstract: Cornelia de Lange syndrome (CdLS) is a rare, multiple congenital anomaly/mental retardation syndrome characterized by varied clinical signs including facial dysmorphism, pre- and post-natal growth defects, small hands and malformations of the upper limbs. Established genetic causes include mutations in the NIPBL (50-60%), SMC1L1 and SMC3 (5%) genes. To detect chromosomal rearrangements pointing to novel positional candidate CdLS genes, we used array-CGH to analyze a subgroup of 24 CdLS patients negative for mutations in the NIPBL and SMC1L1 genes. We identified three carriers of DNA copy number alterations, including a de novo 15q26.2-qter 8-Mb deletion, and two inherited 13q14.2-q14.3 1-Mb deletion and 13q21.32-q21.33 1.5-Mb duplication, not reported among copy number variants. The clinical presentation of all three patients matched the diagnostic criteria for CdLS, and the phenotype of the patient with the 15qter deletion is compared to that of both CdLS and 15qter microdeletion patients.
authors.affiliation: Division of Medical Genetics, San Paolo School of Medicine, University of Milan, Milan, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Gervasini
authors.forename: R
authors.initials: R
authors.lastname: Pfundt
authors.forename: P
authors.initials: P
authors.lastname: Castronovo
authors.forename: S
authors.initials: S
authors.lastname: Russo
authors.forename: G
authors.initials: G
authors.lastname: Roversi
authors.forename: M
authors.initials: M
authors.lastname: Masciadri
authors.forename: D
authors.initials: D
authors.lastname: Milani
authors.forename: G
authors.initials: G
authors.lastname: Zampino
authors.forename: A
authors.initials: A
authors.lastname: Selicorni
authors.forename: E F P M
authors.initials: EF
authors.lastname: Schoenmakers
authors.forename: L
authors.initials: L
authors.lastname: Larizza
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D002872:Chromosome Deletion; D055028:Comparative Genomic Hybridization; D003635:De Lange Syndrome / Q000235:genetics*; D005260:Female; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D011506:Proteins / Q000235:genetics*; D000098550:Structural Maintenance of Chromosome Protein 1
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C487465:NIPBL protein, human; D011506:Proteins; D000098550:Structural Maintenance of Chromosome Protein 1