title: Syndromic craniosynostosis due to complex chromosome 5 rearrangement and MSX2 gene triplication.
abstract: Craniosynostosis is a common birth defect ( approximately 1/3,000 births) resulting from chromosome imbalances, gene mutations or unknown causes. We report a 6-month-old female with multiple sutural synostosis and prenatal onset growth deficiency, developmental delay, facial dysmorphism, congenital heart defect, and inguinal hernia. An integrated approach of standard cytogenetics, mBAND, locus-specific FISH, and 75 kb resolution array-CGH disclosed a complex chromosome 5 rearrangement, resulting in 3 paracentric inversions, 2 between-arm insertions, and partial duplication of 5q35. An extra copy of the MSX2 gene, which maps within the duplicated segment and is mutated in Boston-type craniosynostosis, was confirmed by molecular cytogenetic studies. Our study confirms that early fusion of cranial sutures commonly observed in the dup(5q) syndrome is caused by triplication of the MSX2 gene and strongly supports the crucial role of this gene in the development of craniofacial structures.
authors.affiliation: CSS Hospital, IRCSS, San Giovanni Rotondo and CSS-Mendel Institute, Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Bernardini
authors.forename: Marco
authors.initials: M
authors.lastname: Castori
authors.forename: Anna
authors.initials: A
authors.lastname: Capalbo
authors.forename: Vahe
authors.initials: V
authors.lastname: Mokini
authors.forename: Rita
authors.initials: R
authors.lastname: Mingarelli
authors.forename: Paolo
authors.initials: P
authors.lastname: Simi
authors.forename: Alice
authors.initials: A
authors.lastname: Bertuccelli
authors.forename: Antonio
authors.initials: A
authors.lastname: Novelli
authors.forename: Bruno
authors.initials: B
authors.lastname: Dallapiccola
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D002895:Chromosomes, Human, Pair 5; D003398:Craniosynostoses / Q000175:diagnosis* / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D019066:Facies; D017809:Fatal Outcome; D005260:Female; D020440:Gene Duplication; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D013577:Syndrome; D014314:Trisomy
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C084119:MSX2 protein