Knobloch syndrome: novel mutations in COL18A1, evidence for genetic heterogeneity, and a functionally impaired polymorphism in endostatin.

Details

Serval ID
serval:BIB_B6B7077E3DAE
Type
Article: article from journal or magazin.
Collection
Publications
Title
Knobloch syndrome: novel mutations in COL18A1, evidence for genetic heterogeneity, and a functionally impaired polymorphism in endostatin.
Journal
Human Mutation
Author(s)
Menzel O., Bekkeheien R.C., Reymond A., Fukai N., Boye E., Kosztolanyi G., Aftimos S., Deutsch S., Scott H.S., Olsen B.R., Antonarakis S.E., Guipponi M.
ISSN
1098-1004[electronic], 1059-7794[linking]
Publication state
Published
Issued date
2004
Peer-reviewed
Oui
Volume
23
Number
1
Pages
77-84
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
Publication Status: ppublish
Abstract
Knobloch syndrome (KNO) is an autosomal recessive disorder characterized by high myopia, vitreoretinal degeneration with retinal detachment, and congenital encephalocele. Pathogenic mutations in the COL18A1 gene on 21q22.3 were recently identified in KNO families. Analysis of two unrelated KNO families from Hungary and New Zealand allowed us to confirm the involvement of COL18A1 in the pathogenesis of KNO and to demonstrate the existence of genetic heterogeneity. Two COL18A1 mutations were identified in the Hungarian family: a 1-bp insertion causing a frameshift and a premature in-frame stop codon and an amino acid substitution. This missense variant is located in a conserved amino acid of endostatin, a cleavage product of the carboxy-terminal domain of collagen alpha 1 XVIII. D1437N (D104N in endostatin) likely represents a pathogenic mutation, as we show that the endostatin N104 mutant is impaired in its affinity towards laminin. Linkage to the COL18A1 locus was excluded in the New Zealand family, providing evidence for the existence of a second KNO locus. We named the second unmapped locus for Knobloch syndrome KNO2. Mutation analysis excluded COL15A1, a member of the multiplexin collagen subfamily similar to COL18A1, as being responsible for KNO2.
Keywords
Amino Acid Sequence, Cerebellum/abnormalities, Collagen Type XVIII/genetics, Encephalocele/genetics, Endostatins/genetics, Eye Diseases, Hereditary/genetics, Female, Genetic Variation, Haplotypes, Humans, Male, Models, Genetic, Molecular Sequence Data, Mutation, Myopia/genetics, Pedigree, Polymorphism, Genetic, Retinal Degeneration/genetics, Retinal Detachment/genetics, Sequence Alignment, Syndrome
Pubmed
Web of science
Create date
24/01/2008 15:52
Last modification date
20/08/2019 15:25
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