title: High frequency of submicroscopic chromosomal imbalances in patients with syndromic craniosynostosis detected by a combined approach of microsatellite segregation analysis, multiplex ligation-dependent probe amplification and array-based comparative genome hybridisation.
abstract: We present the first comprehensive study, to our knowledge, on genomic chromosomal analysis in syndromic craniosynostosis. In total, 45 patients with craniosynostotic disorders were screened with a variety of methods including conventional karyotype, microsatellite segregation analysis, subtelomeric multiplex ligation-dependent probe amplification) and whole-genome array-based comparative genome hybridisation. Causative abnormalities were present in 42.2% (19/45) of the samples, and 27.8% (10/36) of the patients with normal conventional karyotype carried submicroscopic imbalances. Our results include a wide variety of imbalances and point to novel chromosomal regions associated with craniosynostosis. The high incidence of pure duplications or trisomies suggests that these are important mechanisms in craniosynostosis, particularly in cases involving the metopic suture.
authors.affiliation: Centro de Estudos do Genoma Humano, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: F S
authors.initials: FS
authors.lastname: Jehee
authors.forename: A C V
authors.initials: AC
authors.lastname: Krepischi-Santos
authors.forename: K M
authors.initials: KM
authors.lastname: Rocha
authors.forename: D P
authors.initials: DP
authors.lastname: Cavalcanti
authors.forename: C A
authors.initials: CA
authors.lastname: Kim
authors.forename: D R
authors.initials: DR
authors.lastname: Bertola
authors.forename: L G
authors.initials: LG
authors.lastname: Alonso
authors.forename: C S
authors.initials: CS
authors.lastname: D'Angelo
authors.forename: J F
authors.initials: JF
authors.lastname: Mazzeu
authors.forename: G
authors.initials: G
authors.lastname: Froyen
authors.forename: D
authors.initials: D
authors.lastname: Lugtenberg
authors.forename: A M
authors.initials: AM
authors.lastname: Vianna-Morgante
authors.forename: C
authors.initials: C
authors.lastname: Rosenberg
authors.forename: M R
authors.initials: MR
authors.lastname: Passos-Bueno
mesh_terms: D002869:Chromosome Aberrations; D020090:Chromosome Segregation; D003398:Craniosynostoses / Q000235:genetics*; D006801:Humans; D007621:Karyotyping; D018895:Microsatellite Repeats; D009693:Nucleic Acid Hybridization / Q000379:methods; D011110:Polymorphism, Genetic