A report on 10 new patients with heterozygous mutations in the COL11A1 gene and a review of genotype-phenotype correlations in type XI collagenopathies.
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.
Majava
Marja
M
Collagen Research Unit, Biocenter, Department of Medical Biochemistry and Molecular Biology, University of Oulu, Oulu, Finland.
Hoornaert
Kristien P
KP
Bartholdi
Deborah
D
Bouma
Mieke C
MC
Bouman
Katelijne
K
Carrera
Marta
M
Devriendt
Koenraad
K
Hurst
Jane
J
Kitsos
George
G
Niedrist
Dunja
D
Petersen
Michael B
MB
Shears
Debbie
D
Stolte-Dijkstra
Irene
I
Van Hagen
J M
JM
Ala-Kokko
Leena
L
Männikkö
Minna
M
Mortier
Geert R
GR
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
D024161:Collagen Type XI