title: Splicing mutations of 54-bp exons in the COL11A1 gene cause Marshall syndrome, but other mutations cause overlapping Marshall/Stickler phenotypes.
abstract: Stickler and Marshall syndromes are dominantly inherited chondrodysplasias characterized by midfacial hypoplasia, high myopia, and sensorineural-hearing deficit. Since the characteristics of these syndromes overlap, it has been argued whether they are distinct entities or different manifestations of a single syndrome. Several mutations causing Stickler syndrome have been found in the COL2A1 gene, and one mutation causing Stickler syndrome and one causing Marshall syndrome have been detected in the COL11A1 gene. We characterize here the genomic structure of the COL11A1 gene. Screening of patients with Stickler, Stickler-like, or Marshall syndrome pointed to 23 novel mutations. Genotypic-phenotypic comparison revealed an association between the Marshall syndrome phenotype and splicing mutations of 54-bp exons in the C-terminal region of the COL11A1 gene. Null-allele mutations in the COL2A1 gene led to a typical phenotype of Stickler syndrome. Some patients, however, presented with phenotypes of both Marshall and Stickler syndromes.
authors.affiliation: Collagen Research Unit, Biocenter and Department of Medical Biochemistry, University of Oulu, Oulu, Finland.
authors.forename: S
authors.initials: S
authors.lastname: Annunen
authors.forename: J
authors.initials: J
authors.lastname: Körkkö
authors.forename: M
authors.initials: M
authors.lastname: Czarny
authors.forename: M L
authors.initials: ML
authors.lastname: Warman
authors.forename: H G
authors.initials: HG
authors.lastname: Brunner
authors.forename: H
authors.initials: H
authors.lastname: Kääriäinen
authors.forename: J B
authors.initials: JB
authors.lastname: Mulliken
authors.forename: L
authors.initials: L
authors.lastname: Tranebjaerg
authors.forename: D G
authors.initials: DG
authors.lastname: Brooks
authors.forename: G F
authors.initials: GF
authors.lastname: Cox
authors.forename: J R
authors.initials: JR
authors.lastname: Cruysberg
authors.forename: M A
authors.initials: MA
authors.lastname: Curtis
authors.forename: S L
authors.initials: SL
authors.lastname: Davenport
authors.forename: C A
authors.initials: CA
authors.lastname: Friedrich
authors.forename: I
authors.initials: I
authors.lastname: Kaitila
authors.forename: M R
authors.initials: MR
authors.lastname: Krawczynski
authors.forename: A
authors.initials: A
authors.lastname: Latos-Bielenska
authors.forename: S
authors.initials: S
authors.lastname: Mukai
authors.forename: B R
authors.initials: BR
authors.lastname: Olsen
authors.forename: N
authors.initials: N
authors.lastname: Shinno
authors.forename: M
authors.initials: M
authors.lastname: Somer
authors.forename: M
authors.initials: M
authors.lastname: Vikkula
authors.forename: J
authors.initials: J
authors.lastname: Zlotogora
authors.forename: D J
authors.initials: DJ
authors.lastname: Prockop
authors.forename: L
authors.initials: L
authors.lastname: Ala-Kokko
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000503:physiopathology; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003094:Collagen / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics*; D005260:Female; D005838:Genotype; D006319:Hearing Loss, Sensorineural / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009216:Myopia / Q000235:genetics / Q000503:physiopathology; D010009:Osteochondrodysplasias / Q000235:genetics* / Q000503:physiopathology; D010641:Phenotype; D012326:RNA Splicing / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion / Q000235:genetics; D013577:Syndrome
chemical_list: D003094:Collagen