title: A report on 10 new patients with heterozygous mutations in the COL11A1 gene and a review of genotype-phenotype correlations in type XI collagenopathies.
abstract: A series of 44 unrelated patients in whom COL2A1 screening demonstrated normal results but whose phenotype was nevertheless highly suggestive of either Stickler syndrome (with ocular involvement) or Marshall syndrome were investigated for mutations in the COL11A1 gene. Heterozygous COL11A1 mutations were found in 10 individuals. A splice site alteration (involving introns 47-55) was present in seven cases, with one in intron 50 (c.3816 + 1G > A) occurring in three patients. Two patients had a different deletion, and a missense mutation (Gly1471Asp) was observed in one case. In 4/10 patients the phenotype was classified as Marshall syndrome because of early-onset severe hearing loss and characteristic facial features. These four patients were all heterozygous for a splice site mutation in intron 50. One of these cases had a type 1 vitreous anomaly despite the presence of a COL11A1 mutation. The remaining 6/10 patients had an overlapping Marshall-Stickler phenotype with less pronounced facial features. None of these had a mutation in the hot spot region of intron 50.
authors.affiliation: Collagen Research Unit, Biocenter, Department of Medical Biochemistry and Molecular Biology, University of Oulu, Oulu, Finland.
authors.forename: Marja
authors.initials: M
authors.lastname: Majava
authors.forename: Kristien P
authors.initials: KP
authors.lastname: Hoornaert
authors.forename: Deborah
authors.initials: D
authors.lastname: Bartholdi
authors.forename: Mieke C
authors.initials: MC
authors.lastname: Bouma
authors.forename: Katelijne
authors.initials: K
authors.lastname: Bouman
authors.forename: Marta
authors.initials: M
authors.lastname: Carrera
authors.forename: Koenraad
authors.initials: K
authors.lastname: Devriendt
authors.forename: Jane
authors.initials: J
authors.lastname: Hurst
authors.forename: George
authors.initials: G
authors.lastname: Kitsos
authors.forename: Dunja
authors.initials: D
authors.lastname: Niedrist
authors.forename: Michael B
authors.initials: MB
authors.lastname: Petersen
authors.forename: Debbie
authors.initials: D
authors.lastname: Shears
authors.forename: Irene
authors.initials: I
authors.lastname: Stolte-Dijkstra
authors.forename: J M
authors.initials: JM
authors.lastname: Van Hagen
authors.forename: Leena
authors.initials: L
authors.lastname: Ala-Kokko
authors.forename: Minna
authors.initials: M
authors.lastname: Männikkö
authors.forename: Geert R
authors.initials: GR
authors.lastname: Mortier
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D024161:Collagen Type XI / Q000235:genetics*; D005260:Female; D030342:Genetic Diseases, Inborn / Q000175:diagnosis*; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D010641:Phenotype
chemical_list: D024161:Collagen Type XI