title: Collagen XI sequence variations in nonsyndromic cleft palate, Robin sequence and micrognathia.
abstract: Cleft palate is a common birth defect, but its etiopathogenesis is mostly unknown. Several studies have shown that cleft palate has a strong genetic component. Robin sequence consists of three of the following four findings: micrognathia, glossoptosis, obstructive apnea, and cleft palate. While cleft palate is mainly nonsyndromic, about 80 percent of Robin sequence cases are associated with syndromes. Mutations in genes coding for cartilage collagens II and XI, COL2A1, COL11A1 and COL11A2, have been shown to cause chondrodysplasias that are commonly associated with Robin sequence, micrognathia or cleft palate. We therefore analyzed a cohort of 24 patients with nonsyndromic Robin sequence, 17 with nonsyndromic cleft palate and 21 with nonsyndromic micrognathia for mutations in COL11A2. A total of 23 Robin sequence patients were also analyzed for mutations in COL2A1 and COL11A1. We detected two disease-associated mutations in patients with Robin sequence, an Arg to stop codon mutation in COL11A2 and a splicing mutation in COL11A1. Two putatively disease-associated sequence variations were found in COL11A1 in Robin sequence patients, one in COL11A2 in a patient with micrognathia and one in COL2A1 in two patients with Robin sequence. The results showed that sequence variations in these genes can play a role in the etiology of Robin sequence, cleft palate and micrognathia but are not common causes of these phenotypes.
authors.affiliation: Collagen Research Unit, Biocenter and Department of Medical Biochemistry and Molecular Biology, University of Oulu, Finland.
authors.forename: Miia
authors.initials: M
authors.lastname: Melkoniemi
authors.forename: Hannele
authors.initials: H
authors.lastname: Koillinen
authors.forename: Minna
authors.initials: M
authors.lastname: Männikkö
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Warman
authors.forename: Tero
authors.initials: T
authors.lastname: Pihlajamaa
authors.forename: Helena
authors.initials: H
authors.lastname: Kääriäinen
authors.forename: Jorma
authors.initials: J
authors.lastname: Rautio
authors.forename: Jyri
authors.initials: J
authors.lastname: Hukki
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Stofko
authors.forename: George J
authors.initials: GJ
authors.lastname: Cisneros
authors.forename: Deborah
authors.initials: D
authors.lastname: Krakow
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Cohn
authors.forename: Juha
authors.initials: J
authors.lastname: Kere
authors.forename: Leena
authors.initials: L
authors.lastname: Ala-Kokko
mesh_terms: D002972:Cleft Palate / Q000235:genetics*; D024043:Collagen Type II / Q000235:genetics*; D024161:Collagen Type XI / Q000235:genetics*; D004252:DNA Mutational Analysis; D017931:DNA Primers; D014644:Genetic Variation; D006801:Humans; D019767:Maxillofacial Abnormalities; D008844:Micrognathism / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D010855:Pierre Robin Syndrome / Q000235:genetics*; D011347:Procollagen / Q000235:genetics*
chemical_list: C499177:COL2A1 protein, human; D024043:Collagen Type II; D024161:Collagen Type XI; D017931:DNA Primers; D011347:Procollagen